2024 |
Richani D, Poljak A, Wang B, Mahbub SB, Biazik J, Campbell JM, et al., 'Oocyte and cumulus cell cooperativity and metabolic plasticity under the direction of oocyte paracrine factors.', Am J Physiol Endocrinol Metab, 326 E366-E381 (2024) [C1]
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2024 |
Calvert L, Martin JH, Anderson AL, Bernstein IR, Burke ND, De Iuliis GN, et al., 'Assessment of the impact of direct in vitro PFAS treatment on mouse spermatozoa.', Reprod Fertil, 5 (2024)
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2024 |
Duchatel RJ, Jackson ER, Parackal SG, Kiltschewskij D, Findlay IJ, Mannan A, et al., 'PI3K/mTOR is a therapeutically targetable genetic dependency in diffuse intrinsic pontine glioma.', J Clin Invest, (2024) [C1]
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2023 |
Fraser BA, Wilkins AL, De Iuliis GN, Rebourcet D, Nixon B, Aitken RJ, 'Development of a model for studying the developmental consequences of oxidative sperm DNA damage by targeting redox-cycling naphthoquinones to the Sertoli cell population.', Free radical biology & medicine, 206 50-62 (2023) [C1]
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Nova |
2023 |
Mulhall JE, Trigg NA, Bernstein IR, Anderson AL, Murray HC, Sipilä P, et al., 'Immortalized mouse caput epididymal epithelial (mECap18) cell line recapitulates the in-vivo environment.', Proteomics, e2300253 (2023) [C1]
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2023 |
Nixon B, Schjenken JE, Burke ND, Skerrett-Byrne DA, Hart HM, De Iuliis GN, et al., 'New horizons in human sperm selection for assisted reproduction', Frontiers in Endocrinology, 14 (2023) [C1]
Male infertility is a commonly encountered pathology that is estimated to be a contributory factor in approximately 50% of couples seeking recourse to assisted reproductive techno... [more]
Male infertility is a commonly encountered pathology that is estimated to be a contributory factor in approximately 50% of couples seeking recourse to assisted reproductive technologies. Upon clinical presentation, such males are commonly subjected to conventional diagnostic andrological practices that rely on descriptive criteria to define their fertility based on the number of morphologically normal, motile spermatozoa encountered within their ejaculate. Despite the virtual ubiquitous adoption of such diagnostic practices, they are not without their limitations and accordingly, there is now increasing awareness of the importance of assessing sperm quality in order to more accurately predict a male¿s fertility status. This realization raises the important question of which characteristics signify a high-quality, fertilization competent sperm cell. In this review, we reflect on recent advances in our mechanistic understanding of sperm biology and function, which are contributing to a growing armory of innovative approaches to diagnose and treat male infertility. In particular we review progress toward the implementation of precision medicine; the robust clinical adoption of which in the setting of fertility, currently lags well behind that of other fields of medicine. Despite this, research shows that the application of advanced technology platforms such as whole exome sequencing and proteomic analyses hold considerable promise in optimizing outcomes for the management of male infertility by uncovering and expanding our inventory of candidate infertility biomarkers, as well as those associated with recurrent pregnancy loss. Similarly, the development of advanced imaging technologies in tandem with machine learning artificial intelligence are poised to disrupt the fertility care paradigm by advancing our understanding of the molecular and biological causes of infertility to provide novel avenues for future diagnostics and treatments.
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Nova |
2023 |
Smyth SP, Nixon B, Skerrett-Byrne DA, Burke ND, Bromfield EG, 'Building an Understanding of Proteostasis in Reproductive Cells: The Impact of Reactive Carbonyl Species on Protein Fate.', Antioxid Redox Signal, (2023) [C1]
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2023 |
Bernstein IR, Nixon B, Lyons JM, Damyanova KB, De Oliveira CS, Mabotuwana NS, et al., 'The hypoxia-inducible factor EPAS1 is required for spermatogonial stem cell function in regenerative conditions', iScience, 26 108424-108424 (2023) [C1]
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Nova |
2023 |
Jackson ER, Duchatel RJ, Staudt DE, Persson ML, Mannan A, Yadavilli S, et al., 'ONC201 in combination with paxalisib for the treatment of H3K27-altered diffuse midline glioma.', Cancer research, CAN-23-0186 (2023) [C1]
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Nova |
2023 |
Staudt DE, Murray HC, Skerrett-Byrne DA, Smith ND, Jamaluddin MFB, Kahl RGS, et al., 'Phospho-heavy-labeled-spiketide FAIMS stepped-CV DDA (pHASED) provides real-time phosphoproteomics data to aid in cancer drug selection (vol 19, 48, 2022)', CLINICAL PROTEOMICS, 20 (2023)
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2023 |
Germon ZP, Sillar JR, Mannan A, Duchatel RJ, Staudt D, Murray HC, et al., 'Blockade of ROS production inhibits oncogenic signaling in acute myeloid leukemia and amplifies response to precision therapies.', Sci Signal, 16 eabp9586 (2023) [C1]
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Nova |
2022 |
Zhang M, Chiozzi RZ, Skerrett-Byrne DA, Veenendaal T, Klumperman J, Heck AJR, et al., 'High Resolution Proteomic Analysis of Subcellular Fractionated Boar Spermatozoa Provides Comprehensive Insights Into Perinuclear Theca-Residing Proteins.', Front Cell Dev Biol, 10 836208 (2022) [C1]
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Nova |
2022 |
Smyth SP, Nixon B, Anderson AL, Murray HC, Martin JH, MacDougall LA, et al., 'Elucidation of the protein composition of mouse seminal vesicle fluid.', Proteomics, 22 e2100227 (2022) [C1]
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Nova |
2022 |
Calvert L, Green MP, De Iuliis GN, Dun MD, Turner BD, Clarke BO, et al., 'Assessment of the Emerging Threat Posed by Perfluoroalkyl and Polyfluoroalkyl Substances to Male Reproduction in Humans', FRONTIERS IN ENDOCRINOLOGY, 12 (2022) [C1]
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Nova |
2022 |
De Oliveira CS, Nixon B, Lord T, 'A scRNA-seq Approach to Identifying Changes in Spermatogonial Stem Cell Gene Expression Following in vitro Culture', FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 10 (2022) [C1]
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Nova |
2022 |
Wei Y-S, Lin W-Z, Wang T-E, Lee W-Y, Li S-H, Lin F-J, et al., 'Polarized epithelium-sperm co-culture system reveals stimulatory factors for the secretion of mouse epididymal quiescin sulfhydryl oxidase 1.', J Reprod Dev, 68 198-208 (2022) [C1]
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Nova |
2022 |
Perera TRW, Skerrett-Byrne DA, Gibb Z, Nixon B, Swegen A, 'The Future of Biomarkers in Veterinary Medicine: Emerging Approaches and Associated Challenges', ANIMALS, 12 (2022) [C1]
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Nova |
2022 |
Martin JH, Nixon B, Cafe SL, Aitken RJ, Bromfield EG, Lord T, 'OXIDATIVE STRESS AND REPRODUCTIVE FUNCTION: Oxidative stress and in vitro ageing of the post-ovulatory oocyte: an update on recent advances in the field', REPRODUCTION, 164 F109-F124 (2022) [C1]
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Nova |
2022 |
Burke ND, Nixon B, Roman SD, Schjenken JE, Walters JLH, Aitken RJ, Bromfield EG, 'Male infertility and somatic health - insights into lipid damage as a mechanistic link', NATURE REVIEWS UROLOGY, 19 727-750 (2022) [C1]
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Nova |
2022 |
Skerrett-Byrne DA, Anderson AL, Bromfield EG, Bernstein IR, Mulhall JE, Schjenken JE, et al., 'Global profiling of the proteomic changes associated with the post-testicular maturation of mouse spermatozoa', Cell Reports, 41 (2022) [C1]
Spermatozoa acquire fertilization potential during passage through a highly specialized region of the extratesticular ductal system known as the epididymis. In the absence of de n... [more]
Spermatozoa acquire fertilization potential during passage through a highly specialized region of the extratesticular ductal system known as the epididymis. In the absence of de novo gene transcription or protein translation, this functional transformation is extrinsically driven via the exchange of varied macromolecular cargo between spermatozoa and the surrounding luminal plasma. Key among these changes is a substantive remodeling of the sperm proteomic architecture, the scale of which has yet to be fully resolved. Here, we have exploited quantitative mass spectrometry-based proteomics to define the extent of changes associated with the maturation of mouse spermatozoa; reporting the identity of >6,000 proteins, encompassing the selective loss and gain of several hundred proteins. Further, we demonstrate epididymal-driven activation of RHOA-mediated signaling pathways is an important component of sperm maturation. These data contribute molecular insights into the complexity of proteomic changes associated with epididymal sperm maturation.
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Nova |
2022 |
Staudt DE, Murray HC, Skerrett-Byrne DA, Smith ND, Jamaluddin MFB, Kahl RGS, et al., 'Phospho-heavy-labeled-spiketide FAIMS stepped-CV DDA (pHASED) provides real-time phosphoproteomics data to aid in cancer drug selection', CLINICAL PROTEOMICS, 19 (2022) [C1]
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Nova |
2022 |
Trigg NA, Skerrett-Byrne DA, Martin JH, De Iuliis GN, Dun MD, Roman SD, et al., 'Quantitative proteomic dataset of mouse caput epididymal epithelial cells exposed to acrylamide in vivo', DATA IN BRIEF, 42 (2022)
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2021 |
Cafe SL, Skerrett-Byrne DA, De Oliveira CS, Nixon B, Oatley MJ, Oatley JM, Lord T, 'A regulatory role for CHD4 in maintenance of the spermatogonial stem cell pool', STEM CELL REPORTS, 16 1555-1567 (2021) [C1]
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Nova |
2021 |
Nixon B, Anderson AL, Bromfield EG, Martin JH, Cafe SL, Skerrett-Byrne DA, et al., 'Post-testicular sperm maturation in the saltwater crocodile Crocodylus porosus: assessing the temporal acquisition of sperm motility', REPRODUCTION FERTILITY AND DEVELOPMENT, 33 530-539 (2021) [C1]
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Nova |
2021 |
Cafe SL, Nixon B, Ecroyd H, Martin JH, Skerrett-Byrne DA, Bromfield EG, 'Proteostasis in the Male and Female Germline: A New Outlook on the Maintenance of Reproductive Health', FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 9 (2021) [C1]
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Nova |
2021 |
Mannan A, Germon ZP, Chamberlain J, Sillar JR, Nixon B, Dun MD, 'Reactive oxygen species in acute lymphoblastic leukaemia: Reducing radicals to refine responses', Antioxidants, 10 (2021) [C1]
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Nova |
2021 |
Johnston SD, Lever J, McLeod R, Qualischefski E, Madrigal-Valverde M, Nixon B, 'Assisted breeding technology in the saltwater crocodile Crocodylus porosus: a review and look to the future', REPRODUCTION FERTILITY AND DEVELOPMENT, 33 503-518 (2021) [C1]
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Nova |
2021 |
Murray HC, Enjeti AK, Kahl RGS, Flanagan HM, Sillar J, Skerrett-Byrne DA, et al., 'Quantitative phosphoproteomics uncovers synergy between DNA-PK and FLT3 inhibitors in acute myeloid leukaemia', LEUKEMIA, 35 1782-1787 (2021)
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2021 |
Aitken RJ, Curry BJ, Shokri S, Pujianto DA, Gavriliouk D, Gibb Z, et al., 'Evidence that extrapancreatic insulin production is involved in the mediation of sperm survival', Molecular and Cellular Endocrinology, 526 (2021) [C1]
Evidence is presented for expression of the insulin receptor on the surface of mammalian spermatozoa as well as transcripts for the receptor substrate adaptor proteins (IRS1-4) ne... [more]
Evidence is presented for expression of the insulin receptor on the surface of mammalian spermatozoa as well as transcripts for the receptor substrate adaptor proteins (IRS1-4) needed to mediate insulin action. Exposure to this hormone resulted in insulin receptor phosphorylation (pTyr972), activation of AKT (pSer473) and the stimulation of sperm motility. Intriguingly, the male germ line is also shown to be capable of generating insulin, possessing the relevant mRNA transcript and expressing strong immunocytochemical signals for both insulin and C-peptide. Insulin could be released from the spermatozoa by sonication in a concentration-dependent manner but was not secreted in response to glucose, fructose or stimulation with progesterone. However, insulin release could be induced by factors present in human uterine lavages. Furthermore, the endometrium was also shown to possess the machinery for insulin production and action (mRNA, insulin, C-peptide, proprotein convertase and insulin receptor), releasing insulin into the uterine lumen prior to ovulation. These studies emphasize the fundamental importance of extra-pancreatic insulin in regulating the reproductive process, particularly in the support of spermatozoa on their perilous voyage to the site of fertilization.
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Nova |
2021 |
Skerrett-Byrne DA, Bromfield EG, Murray HC, Jamaluddin MFB, Jarnicki AG, Fricker M, et al., 'Time-resolved proteomic profiling of cigarette smoke-induced experimental chronic obstructive pulmonary disease', Respirology, 26 960-973 (2021) [C1]
Background and objective: Chronic obstructive pulmonary disease (COPD) is the third leading cause of illness and death worldwide. Current treatments aim to control symptoms with n... [more]
Background and objective: Chronic obstructive pulmonary disease (COPD) is the third leading cause of illness and death worldwide. Current treatments aim to control symptoms with none able to reverse disease or stop its progression. We explored the major molecular changes in COPD pathogenesis. Methods: We employed quantitative label-based proteomics to map the changes in the lung tissue proteome of cigarette smoke-induced experimental COPD that is induced over 8 weeks and progresses over 12 weeks. Results: Quantification of 7324 proteins enabled the tracking of changes to the proteome. Alterations in protein expression profiles occurred in the induction phase, with 18 and 16 protein changes at 4- and 6-week time points, compared to age-matched controls, respectively. Strikingly, 269 proteins had altered expression after 8 weeks when the hallmark pathological features of human COPD emerge, but this dropped to 27 changes at 12 weeks with disease progression. Differentially expressed proteins were validated using other mouse and human COPD bronchial biopsy samples. Major changes in RNA biosynthesis (heterogeneous nuclear ribonucleoproteins C1/C2 [HNRNPC] and RNA-binding protein Musashi homologue 2 [MSI2]) and modulators of inflammatory responses (S100A1) were notable. Mitochondrial dysfunction and changes in oxidative stress proteins also occurred. Conclusion: We provide a detailed proteomic profile, identifying proteins associated with the pathogenesis and disease progression of COPD establishing a platform to develop effective new treatment strategies.
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Nova |
2021 |
Skerrett-Byrne DA, Trigg NA, Bromfield EG, Dun MD, Bernstein IR, Anderson AL, et al., 'Proteomic dissection of the impact of environmental exposures on mouse seminal vesicle function', Molecular and Cellular Proteomics, 20 (2021) [C1]
Seminal vesicles are an integral part of the male reproductive accessory gland system. They produce a complex array of secretions containing bioactive constituents that support ga... [more]
Seminal vesicles are an integral part of the male reproductive accessory gland system. They produce a complex array of secretions containing bioactive constituents that support gamete function and promote reproductive success, with emerging evidence suggesting these secretions are influenced by our environment. Despite their significance, the biology of seminal vesicles remains poorly defined. Here, we complete the first proteomic assessment of mouse seminal vesicles and assess the impact of the reproductive toxicant acrylamide. Mice were administered acrylamide (25 mg/kg bw/day) or control daily for five consecutive days prior to collecting seminal vesicle tissue. A total of 5013 proteins were identified in the seminal vesicle proteome with bioinformatic analyses identifying cell proliferation, protein synthesis, cellular death, and survival pathways as prominent biological processes. Secreted proteins were among the most abundant, and several proteins are linked with seminal vesicle phenotypes. Analysis of the effect of acrylamide on the seminal vesicle proteome revealed 311 differentially regulated (FC ± 1.5, p = 0.05, 205 up-regulated, 106 downregulated) proteins, orthogonally validated via immunoblotting and immunohistochemistry. Pathways that initiate protein synthesis to promote cellular survival were prominent among the dysregulated pathways, and rapamycin-insensitive companion of mTOR (RICTOR, p = 6.69E-07) was a top-ranked upstream driver. Oxidative stress was implicated as contributing to protein changes, with acrylamide causing an increase in 8-OHdG in seminal vesicle epithelial cells (fivefold increase, p = 0.016) and the surrounding smooth muscle layer (twofold increase, p = 0.043). Additionally, acrylamide treatment caused a reduction in seminal vesicle secretion weight (36% reduction, p = 0.009) and total protein content (25% reduction, p = 0.017). Together these findings support the interpretation that toxicant exposure influences male accessory gland physiology and highlights the need to consider the response of all male reproductive tract tissues when interpreting the impact of environmental stressors on male reproductive function.
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Nova |
2021 |
Skerrett-Byrne DA, Anderson AL, Hulse L, Wass C, Dun MD, Bromfield EG, et al., 'Proteomic analysis of koala (phascolarctos cinereus) spermatozoa and prostatic bodies', Proteomics, 21 (2021) [C1]
The aims of this study were to investigate the proteome of koala spermatozoa and that of the prostatic bodies with which they interact during ejaculation. For this purpose, sperma... [more]
The aims of this study were to investigate the proteome of koala spermatozoa and that of the prostatic bodies with which they interact during ejaculation. For this purpose, spermatozoa and prostatic bodies were fractionated from the semen of four male koalas and analysed by HPLC MS/MS. This strategy identified 744 sperm and 1297 prostatic body proteins, which were subsequently attributed to 482 and 776 unique gene products, respectively. Gene ontology curation of the sperm proteome revealed an abundance of proteins mapping to the canonical sirtuin and 14-3-3 signalling pathways. By contrast, protein ubiquitination and unfolded protein response pathways dominated the equivalent analysis of proteins uniquely identified in prostatic bodies. Koala sperm proteins featured an enrichment of those mapping to the functional categories of cellular compromise/inflammatory response, whilst those of the prostatic body revealed an over-representation of molecular chaperone and stress-related proteins. Cross-species comparisons demonstrated that the koala sperm proteome displays greater conservation with that of eutherians (human; 93%) as opposed to reptile (crocodile; 39%) and avian (rooster; 27%) spermatozoa. Together, this work contributes to our overall understanding of the core sperm proteome and has identified biomarkers that may contribute to the exceptional longevity of koala spermatozoa during ex vivo storage.
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Nova |
2021 |
Duchatel RJ, Mannan A, Woldu AS, Hawtrey T, Hindley PA, Douglas AM, et al., 'Preclinical and clinical evaluation of German-sourced ONC201 for the treatment of H3K27M-mutant diffuse intrinsic pontine glioma.', Neuro-oncology advances, 3 vdab169 (2021) [C1]
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Nova |
2021 |
Walters JLH, Anderson AL, da Silva SJM, Aitken RJ, De Iuliis GN, Sutherland JM, et al., 'Mechanistic insight into the regulation of lipoxygenase-driven lipid peroxidation events in human spermatozoa and their impact on male fertility', Antioxidants, 10 1-19 (2021) [C1]
A prevalent cause of sperm dysfunction in male infertility patients is the overproduction of reactive oxygen species, an attendant increase in lipid peroxidation and the productio... [more]
A prevalent cause of sperm dysfunction in male infertility patients is the overproduction of reactive oxygen species, an attendant increase in lipid peroxidation and the production of cyto-toxic reactive carbonyl species such as 4-hydroxynonenal. Our previous studies have implicated arachidonate 15-lipoxygenase (ALOX15) in the production of 4-hydroxynonenal in developing germ cells. Here, we have aimed to develop a further mechanistic understanding of the lipoxygen-ase-lipid peroxidation pathway in human spermatozoa. Through pharmacological inhibition studies, we identified a protective role for phospholipase enzymes in the liberation of peroxidised polyunsaturated fatty acids from the human sperm membrane. Our results also revealed that arachi-donic acid, linoleic acid and docosahexanoic acid are key polyunsaturated fatty acid substrates for ALOX15. Upon examination of ALOX15 in the spermatozoa of infertile patients compared to their normozoospermic counterparts, we observed significantly elevated levels of ALOX15 protein abundance in the infertile population and an increase in 4-hydroxynonenal adducts. Collectively, these data confirm the involvement of ALOX15 in the oxidative stress cascade of human spermatozoa and support the notion that increased ALOX15 abundance in sperm cells may accentuate membrane lipid peroxidation and cellular dysfunction, ultimately contributing to male infertility.
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Nova |
2021 |
Skerrett-Byrne DA, Nixon B, Bromfield EG, Breen J, Trigg NA, Stanger SJ, et al., 'Transcriptomic analysis of the seminal vesicle response to the reproductive toxicant acrylamide', BMC Genomics, 22 (2021) [C1]
Background: The seminal vesicles synthesise bioactive factors that support gamete function, modulate the female reproductive tract to promote implantation, and influence developme... [more]
Background: The seminal vesicles synthesise bioactive factors that support gamete function, modulate the female reproductive tract to promote implantation, and influence developmental programming of offspring phenotype. Despite the significance of the seminal vesicles in reproduction, their biology remains poorly defined. Here, to advance understanding of seminal vesicle biology, we analyse the mouse seminal vesicle transcriptome under normal physiological conditions and in response to acute exposure to the reproductive toxicant acrylamide. Mice were administered acrylamide (25 mg/kg bw/day) or vehicle control daily for five consecutive days prior to collecting seminal vesicle tissue 72 h following the final injection. Results: A total of 15,304 genes were identified in the seminal vesicles with those encoding secreted proteins amongst the most abundant. In addition to reproductive hormone pathways, functional annotation of the seminal vesicle transcriptome identified cell proliferation, protein synthesis, and cellular death and survival pathways as prominent biological processes. Administration of acrylamide elicited 70 differentially regulated (fold-change =1.5 or = 0.67) genes, several of which were orthogonally validated using quantitative PCR. Pathways that initiate gene and protein synthesis to promote cellular survival were prominent amongst the dysregulated pathways. Inflammation was also a key transcriptomic response to acrylamide, with the cytokine, Colony stimulating factor 2 (Csf2) identified as a top-ranked upstream driver and inflammatory mediator associated with recovery of homeostasis. Early growth response (Egr1), C-C motif chemokine ligand 8 (Ccl8), and Collagen, type V, alpha 1 (Col5a1) were also identified amongst the dysregulated genes. Additionally, acrylamide treatment led to subtle changes in the expression of genes that encode proteins secreted by the seminal vesicle, including the complement regulator, Complement factor b (Cfb). Conclusions: These data add to emerging evidence demonstrating that the seminal vesicles, like other male reproductive tract tissues, are sensitive to environmental insults, and respond in a manner with potential to exert impact on fetal development and later offspring health.
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Nova |
2021 |
Trigg NA, Skerrett-Byrne DA, Xavier MJ, Zhou W, Anderson AL, Stanger SJ, et al., 'Acrylamide modulates the mouse epididymal proteome to drive alterations in the sperm small non-coding RNA profile and dysregulate embryo development', Cell Reports, 37 (2021) [C1]
Paternal exposure to environmental stressors elicits distinct changes to the sperm sncRNA profile, modifications that have significant post-fertilization consequences. Despite thi... [more]
Paternal exposure to environmental stressors elicits distinct changes to the sperm sncRNA profile, modifications that have significant post-fertilization consequences. Despite this knowledge, there remains limited mechanistic understanding of how paternal exposures modify the sperm sncRNA landscape. Here, we report the acute sensitivity of the sperm sncRNA profile to the reproductive toxicant acrylamide. Furthermore, we trace the differential accumulation of acrylamide-responsive sncRNAs to coincide with sperm transit of the proximal (caput) segment of the epididymis, wherein acrylamide exposure alters the abundance of several transcription factors implicated in the expression of acrylamide-sensitive sncRNAs. We also identify extracellular vesicles secreted from the caput epithelium in relaying altered sncRNA profiles to maturing spermatozoa and dysregulated gene expression during early embryonic development following fertilization by acrylamide-exposed spermatozoa. These data provide mechanistic links to account for how environmental insults can alter the sperm epigenome and compromise the transcriptomic profile of early embryos.
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Nova |
2021 |
Peters AE, Caban SJ, McLaughlin EA, Roman SD, Bromfield EG, Nixon B, Sutherland JM, 'The Impact of Aging on Macroautophagy in the Pre-ovulatory Mouse Oocyte', Frontiers in Cell and Developmental Biology, 9 (2021) [C1]
Accompanying the precipitous age-related decline in human female fertility is an increase in the proportion of poor-quality oocytes within the ovary. The macroautophagy pathway, a... [more]
Accompanying the precipitous age-related decline in human female fertility is an increase in the proportion of poor-quality oocytes within the ovary. The macroautophagy pathway, an essential protein degradation mechanism responsible for maintaining cell health, has not yet been thoroughly investigated in this phenomenon. The aim of this study was to characterize the macroautophagy pathway in an established mouse model of oocyte aging using in-depth image analysis-based methods and to determine mechanisms that account for the observed changes. Three autophagy pathway markers were selected for assessment of gene and protein expression in this model: Beclin 1; an initiator of autophagosome formation, Microtubule-associated protein 1 light chain 3B; a constituent of the autophagosome membrane, and lysosomal-associated membrane protein 1; a constituent of the lysosome membrane. Through quantitative image analysis of immunolabeled oocytes, this study revealed impairment of the macroautophagy pathway in the aged oocyte with an attenuation of both autophagosome and lysosome number. Additionally, an accumulation of amphisomes greater than 10 µm2 in area were observed in aging oocytes, and this accumulation was mimicked in oocytes treated with lysosomal inhibitor chloroquine. Overall, these findings implicate lysosomal dysfunction as a prominent mechanism by which these age-related changes may occur and highlight the importance of macroautophagy in maintaining mouse pre-ovulatory oocyte quality. This provides a basis for further investigation of dysfunctional autophagy in poor oocyte quality and for the development of therapeutic or preventative strategies to aid in the maintenance of pre-ovulatory oocyte health.
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Nova |
2021 |
Fraser B, Peters AE, Sutherland JM, Liang M, Rebourcet D, Nixon B, Aitken RJ, 'Biocompatible Nanomaterials as an Emerging Technology in Reproductive Health; a Focus on the Male', Frontiers in Physiology, 12 (2021) [C1]
A growing body of research has confirmed that nanoparticle (NP) systems can enhance delivery of therapeutic and imaging agents as well as prevent potentially damaging systemic exp... [more]
A growing body of research has confirmed that nanoparticle (NP) systems can enhance delivery of therapeutic and imaging agents as well as prevent potentially damaging systemic exposure to these agents by modifying the kinetics of their release. With a wide choice of NP materials possessing different properties and surface modification options with unique targeting agents, bespoke nanosystems have been developed for applications varying from cancer therapeutics and genetic modification to cell imaging. Although there remain many challenges for the clinical application of nanoparticles, including toxicity within the reproductive system, some of these may be overcome with the recent development of biodegradable nanoparticles that offer increased biocompatibility. In recognition of this potential, this review seeks to present recent NP research with a focus on the exciting possibilities posed by the application of biocompatible nanomaterials within the fields of male reproductive medicine, health, and research.
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Nova |
2021 |
Nixon B, Anderson AL, Bromfield EG, Martin JH, Lord T, Cafe SL, et al., 'Gross and microanatomy of the male reproductive duct system of the saltwater crocodile Crocodylus porosus', REPRODUCTION FERTILITY AND DEVELOPMENT, 33 540-554 (2021) [C1]
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Nova |
2021 |
Miller RR, Beranek F, Anderson AL, Johnston SD, Nixon B, 'Plasma and acrosomal membrane lipid content of saltwater crocodile spermatozoa', REPRODUCTION FERTILITY AND DEVELOPMENT, 33 596-604 (2021) [C1]
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Nova |
2021 |
Ruhen O, Qu X, Jamaluddin MFB, Salomon C, Gandhi A, Millward M, et al., 'Dynamic Landscape of Extracellular Vesicle-Associated Proteins Is Related to Treatment Response of Patients with Metastatic Breast Cancer', MEMBRANES, 11 (2021) [C1]
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Nova |
2021 |
Trigg NA, Stanger SJ, Zhou W, Skerrett-Byrne DA, Sipilä P, Dun MD, et al., 'A novel role for milk fat globule-EGF factor 8 protein (MFGE8) in the mediation of mouse sperm extracellular vesicle interactions', Proteomics, 21 (2021) [C1]
Spermatozoa transition to functional maturity as they are conveyed through the epididymis, a highly specialized region of the male excurrent duct system. Owing to their transcript... [more]
Spermatozoa transition to functional maturity as they are conveyed through the epididymis, a highly specialized region of the male excurrent duct system. Owing to their transcriptionally and translationally inert state, this transformation into fertilization competent cells is driven by complex mechanisms of intercellular communication with the secretory epithelium that delineates the epididymal tubule. Chief among these mechanisms are the release of extracellular vesicles (EV), which have been implicated in the exchange of varied macromolecular cargo with spermatozoa. Here, we describe the optimization of a tractable cell culture model to study the mechanistic basis of sperm¿extracellular vesicle interactions. In tandem with receptor inhibition strategies, our data demonstrate the importance of milk fat globule-EGF factor 8 (MFGE8) protein in mediating the efficient exchange of macromolecular EV cargo with mouse spermatozoa; with the MFGE8 integrin-binding Arg-Gly-Asp (RGD) tripeptide motif identified as being of particular importance. Specifically, complementary strategies involving MFGE8 RGD domain ablation, competitive RGD-peptide inhibition and antibody-masking of alpha V integrin receptors, all significantly inhibited the uptake and redistribution of EV-delivered proteins into immature mouse spermatozoa. These collective data implicate the MFGE8 ligand and its cognate integrin receptor in the mediation of the EV interactions that underpin sperm maturation.
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Nova |
2020 |
Liu G, Baird AW, Parsons MJ, Fan K, Skerrett-Byrne DA, Nair PM, et al., 'Platelet activating factor receptor acts to limit colitis-induced liver inflammation', FASEB JOURNAL, 34 7718-7732 (2020) [C1]
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Nova |
2020 |
Nixon B, Cafe SL, Eamens AL, De Iuliis GN, Bromfield EG, Martin JH, et al., 'Molecular insights into the divergence and diversity of post-testicular maturation strategies', Molecular and Cellular Endocrinology, 517 110955-110955 (2020) [C1]
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Nova |
2020 |
Fennell KA, Busby RGG, Li S, Bodden C, Stanger SJ, Nixon B, et al., 'Limitations to intergenerational inheritance: subchronic paternal stress preconception does not influence offspring anxiety', Scientific Reports, 10 (2020) [C1]
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Nova |
2020 |
Aitken RJ, De Iuliis GN, Nixon B, 'The Sins of Our Forefathers: Paternal Impacts on De Novo Mutation Rate and Development', Annual Review of Genetics, 54 1-24 (2020) [C1]
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Nova |
2020 |
Griffin RA, Swegen A, Baker M, Aitken RJ, Skerrett-Byrne DA, Rodriguez AS, et al., 'Mass spectrometry reveals distinct proteomic profiles in high- And low-quality stallion spermatozoa', Reproduction, 160 695-707 (2020) [C1]
The horse breeding industry relies upon optimal stallion fertility. Conventional sperm assessments provide limited information regarding ejaculate quality and are not individually... [more]
The horse breeding industry relies upon optimal stallion fertility. Conventional sperm assessments provide limited information regarding ejaculate quality and are not individually predictive of fertilizing potential. The aim of this study was to harness mass spectrometry to compare the proteomic profiles of high- and low-quality stallion spermatozoa, with the ultimate goal of identifying fertility biomarker candidates. Extended stallion semen (n = 12) was fractionated using Percoll density gradients to isolate low-quality and high-quality sperm populations. Motility and morphological assessments were carried out, and proteomic analyses was conducted using UHPLC-MS/MS. High-quality spermatozoa recorded higher total (95.2 ± 0.52% vs 70.6 ± 4.20%; P = 0.001) and progressive motilities (43.4 ± 3.42% vs 27.3 ± 4.32%; P = 0.05), and a higher proportion of morphologically normal cells (50.2 ± 4.34% vs 38.8 ± 2.72%; P = 0.05). In total, 1069 proteins were quantified by UHPLC-MS/MS, of which 22 proteins were significantly more abundant in the high-quality sperm population (P = 0.05). A-kinase anchor protein 4 (AKAP4) and Hexokinase 1 (HK1) were considered possible biomarker candidates and their differential expression was confirmed by immunoblot. Protein expression was significantly correlated with total (AKAP4 R2 = 0.38, P = 0.01; HK1 R2 = 0.46, P = 0.001) and progressive motilities (AKAP4 R2 = 0.51, P = 0.001; HK1 R2 = 0.55, P = 0.01), percentage rapid (AKAP4 R2 = 0.29, P = 0.05; HK1 R2 = 0.58, P = 0.001), straight-line velocity (HK1 R2 = 0.50, P = 0.01) and straightness (HK1 R2 = 0.40, P = 0.01). Furthermore, AKAP4 was highly susceptible to adduction by 4-hydroxynonenal (4HNE), which resulted in a global reduction in the phosphorylation profiles following capacitation. In conclusion, the proteomic profiles of high- and low-quality stallion spermatozoa differ substantially, and proteins such as AKAP4 and HK1 could serve as biomarkers of ejaculate quality.
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2020 |
Walters JLH, Gadella BM, Sutherland JM, Nixon B, Bromfield EG, 'Male Infertility: Shining a Light on Lipids and Lipid-Modulating Enzymes in the Male Germline', Journal of Clinical Medicine, 9 (2020) [C1]
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2020 |
Cafe SL, Nixon B, Dun MD, Roman SD, Bernstein IR, Bromfield EG, 'Oxidative Stress Dysregulates Protein Homeostasis within the Male Germ Line', Antioxidants and Redox Signaling, 32 487-503 (2020) [C1]
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2020 |
Campbell L, Cafe SL, Upton R, Doody JS, Nixon B, Clulow J, Clulow S, 'A model protocol for the cryopreservation and recovery of motile lizard sperm using the phosphodiesterase inhibitor caffeine', CONSERVATION PHYSIOLOGY, 8 (2020) [C1]
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2020 |
Peters AE, Mihalas BP, Bromfield EG, Roman SD, Nixon B, Sutherland JM, 'Autophagy in Female Fertility: A Role in Oxidative Stress and Aging', ANTIOXIDANTS & REDOX SIGNALING, 32 550-568 (2020) [C1]
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2020 |
Nowicka-bauer K, Nixon B, 'Molecular changes induced by oxidative stress that impair human sperm motility', Antioxidants, 9 (2020) [C1]
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2020 |
Tamessar CT, Trigg NA, Nixon B, Skerrett-Byrne DA, Sharkey DJ, Robertson SA, et al., 'Roles of male reproductive tract extracellular vesicles in reproduction', AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, 85 (2020) [C1]
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2020 |
Mihalas BP, Redgrove KA, Bernstein IR, Robertson MJ, McCluskey A, Nixon B, et al., 'Dynamin 2-dependent endocytosis is essential for mouse oocyte development and fertility', FASEB Journal, 34 5162-5177 (2020) [C1]
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2020 |
Chu C, Yu L, Henry-Berger J, Ru Y-F, Kocer A, Champroux A, et al., 'Knockout of glutathione peroxidase 5 down-regulates the piRNAs in the caput epididymidis of aged mice.', Asian Journal of Andrology, 22 590-601 (2020) [C1]
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2020 |
Cafe SL, Anderson AL, Nixon B, 'In vitro Induction and Detection of Acrosomal Exocytosis in Human Spermatozoa', BIO-PROTOCOL, 10 (2020)
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2020 |
Fraser BA, Miller K, Trigg NA, Smith ND, Western PS, Nixon B, Aitken RJ, 'A novel approach to nonsurgical sterilization; application of menadione-modified gonocyte-targeting M13 bacteriophage for germ cell ablation in utero', PHARMACOLOGY RESEARCH & PERSPECTIVES, 8 (2020) [C1]
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2020 |
Stanger SJ, Bernstein IR, Anderson AL, Hutcheon K, Dun MD, Eamens AL, Nixon B, 'The abundance of a transfer RNA-derived RNA fragment small RNA subpopulation is enriched in cauda spermatozoa', ExRNA, 2 (2020) [C1]
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2020 |
Dun MD, Mannan A, Rigby CJ, Butler S, Toop HD, Beck D, et al., 'Shwachman Bodian Diamond syndrome (SBDS) protein is a direct inhibitor of protein phosphatase 2A (PP2A) activity and overexpressed in acute myeloid leukaemia', Leukemia, 34 3393-3397 (2020) [C1]
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2020 |
Lord T, Nixon B, 'Metabolic Changes Accompanying Spermatogonial Stem Cell Differentiation', Developmental Cell, 52 399-411 (2020) [C1]
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2019 |
Nixon B, De Iuliis GN, Dun MD, Zhou W, Trigg NA, Eamens AL, 'Profiling of epididymal small non-protein-coding RNAs', Andrology, 7 669-680 (2019) [C1]
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2019 |
Martin JH, Aitken RJ, Bromfield E, Cafe SL, Sutherland JM, Frost ER, et al., 'Investigation into the presence and functional significance of proinsulin C-peptide in the female germline', Biology of Reproduction, 100 1275-1289 (2019) [C1]
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2019 |
Nixon B, De Iuliis GN, Hart HM, Zhou W, Mathe A, Bernstein IR, et al., 'Proteomic profiling of mouse epididymosomes reveals their contributions to post-testicular sperm maturation', Molecular and Cellular Proteomics, 18 S91-S108 (2019) [C1]
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2019 |
Gaikwad AS, Anderson AL, Merriner DJ, O'Connor AE, Houston BJ, Aitken RJ, et al., 'GLIPR1L1 is an IZUMO-binding protein required for optimal fertilization in the mouse.', BMC Biology, 17 (2019) [C1]
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2019 |
Houston BJ, Nixon B, McEwan KE, Martin J, King BV, Aitken RJ, De Iuliis GN, 'Whole-body exposures to radiofrequency-electromagnetic energy can cause DNA damage in mouse spermatozoa via an oxidative mechanism', Scientific Reports, 9 (2019) [C1]
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2019 |
Brown P, RELISH Consortium, Zhou Y, 'Large expert-curated database for benchmarking document similarity detection in biomedical literature search', Database, 2019 (2019) [C1]
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2019 |
Duchatel RJ, Jackson ER, Alvaro F, Nixon B, Hondermarck H, Dun MD, 'Signal Transduction in Diffuse Intrinsic Pontine Glioma', PROTEOMICS, 19 (2019) [C1]
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2019 |
Nixon B, Johnston SD, Skerrett-Byrne DA, Anderson AL, Stanger SJ, Bromfield EG, et al., 'Modification of Crocodile Spermatozoa Refutes the Tenet That Post-testicular Sperm Maturation Is Restricted To Mammals', MOLECULAR & CELLULAR PROTEOMICS, 18 S59-S76 (2019) [C1]
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2019 |
Nixon B, Bernstein IR, Cafe SL, Delehedde M, Sergeant N, Anderson AL, et al., 'A Kinase Anchor Protein 4 is vulnerable to oxidative adduction in male germ cells', Frontiers in Cell and Developmental Biology, 7 (2019) [C1]
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2019 |
Zhou W, Stanger SJ, Anderson AL, Bernstein IR, De Iuliis GN, McCluskey A, et al., 'Mechanisms of tethering and cargo transfer during epididymosome-sperm interactions.', BMC biology, 17 35-35 (2019) [C1]
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2019 |
Bromfield E, Walters JLH, Cafe S, Bernstein I, Stanger SR, Anderson AL, et al., 'Differential cell death decisions in the testis: evidence for an exclusive window of ferroptosis in round spermatids', Molecular Human Reproduction, 25 241-256 (2019) [C1]
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2019 |
Xavier MJ, Roman SD, Aitken RJ, Nixon B, 'Transgenerational inheritance: how impacts to the epigenetic and genetic information of parents affect offspring health', HUMAN REPRODUCTION UPDATE, 25 519-541 (2019) [C1]
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2019 |
Martin JH, Aitken RJ, Bromfield EG, Nixon B, 'DNA damage and repair in the female germline: contributions to ART.', Human Reproduction Update, 25 180-201 (2019) [C1]
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2019 |
Mihalas BP, Camlin NJ, Xavier MJ, Peters AE, Holt JE, Sutherland JM, et al., 'The small non-coding RNA profile of mouse oocytes is modified during aging', AGING-US, 11 2968-2997 (2019) [C1]
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2019 |
Xavier MJ, Nixon B, Roman SD, Scott RJ, Drevet JR, Aitken RJ, 'Paternal impacts on development: Identification of genomic regions vulnerable to oxidative DNA damage in human spermatozoa', Human Reproduction, 34 1876-1890 (2019) [C1]
STUDY QUESTION: Do all regions of the paternal genome within the gamete display equivalent vulnerability to oxidative DNA damage? SUMMARY ANSWER: Oxidative DNA damage is not rando... [more]
STUDY QUESTION: Do all regions of the paternal genome within the gamete display equivalent vulnerability to oxidative DNA damage? SUMMARY ANSWER: Oxidative DNA damage is not randomly distributed in mature human spermatozoa but is instead targeted, with particular chromosomes being especially vulnerable to oxidative stress. WHAT IS KNOWN ALREADY: Oxidative DNA damage is frequently encountered in the spermatozoa of male infertility patients. Such lesions can influence the incidence of de novo mutations in children, yet it remains to be established whether all regions of the sperm genome display equivalent susceptibility to attack by reactive oxygen species. STUDY DESIGN, SIZE, DURATION: Human spermatozoa obtained from normozoospermic males (n = 8) were split into equivalent samples and subjected to either hydrogen peroxide (H2O2) treatment or vehicle controls before extraction of oxidized DNA using a modified DNA immunoprecipitation (MoDIP) protocol. Specific regions of the genome susceptible to oxidative damage were identified by next-generation sequencing and validated in the spermatozoa of normozoospermic males (n = 18) and in patients undergoing infertility evaluation (n = 14). PARTICIPANTS/MATERIALS, SETTING, METHODS: Human spermatozoa were obtained from normozoospermic males and divided into two identical samples prior to being incubated with either H2O2 (5 mm, 1 h) to elicit oxidative stress or an equal volume of vehicle (untreated controls). Alternatively, spermatozoa were obtained from fertility patients assessed as having high basal levels of oxidative stress within their spermatozoa. All semen samples were subjected to MoDIP to selectively isolate oxidized DNA, prior to sequencing of the resultant DNA fragments using a next-generation whole-genomic sequencing platform. Bioinformatic analysis was then employed to identify genomic regions vulnerable to oxidative damage, several of which were selected for real-time quantitative PCR (qPCR) validation. MAIN RESULTS AND THE ROLE OF CHANCE: Approximately 9000 genomic regions, 150-1000 bp in size, were identified as highly vulnerable to oxidative damage in human spermatozoa. Specific chromosomes showed differential susceptibility to damage, with chromosome 15 being particularly sensitive to oxidative attack while the sex chromosomes were protected. Susceptible regions generally lay outside protamine-and histone-packaged domains. Furthermore, we confirmed that these susceptible genomic sites experienced a dramatic (2-15-fold) increase in their burden of oxidative DNA damage in patients undergoing infertility evaluation compared to normal healthy donors. LIMITATIONS, REASONS FOR CAUTION: The limited number of samples analysed in this study warrants external validation, as do the implications of our findings. Selection of male fertility patients was based on high basal levels of oxidative stress within their spermatozoa as opposed to specific sub-classes of male factor infertility. WIDER IMPLICATIONS OF THE FINDINGS: The identification of genomic regions susceptible to oxidation in the male germ line will be of value in focusing future analyses into the mutational load carried by children in response to paternal factors such as age, the treatment of male infertility using ART and paternal exposure to environmental toxicants. STUDY FUNDING/COMPETING INTEREST(S): Project support was provided by the University of Newcastle's (UoN) Priority Research Centre for Reproductive Science. M.J.X. was a recipient of a UoN International Postgraduate Research Scholarship. B.N. is the recipient of a National Health and Medical Research Council of Australia Senior Research Fellowship. Authors declare no conflict of interest.
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2019 |
Trigg NA, Eamens AL, Nixon B, 'The contribution of epididymosomes to the sperm small RNA profile.', Reproduction (Cambridge, England), 157 R209-R223 (2019) [C1]
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2018 |
Zhou W, De Iuliis GN, Dun MD, Nixon B, 'Characteristics of the epididymal luminal environment responsible for sperm maturation and storage', Frontiers in Endocrinology, 9 (2018) [C1]
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Nova |
2018 |
Wang TE, Li SH, Minabe S, Andreson AL, Dun MD, Maeda KI, et al., 'Mouse quiescin sulfhydryl oxidases exhibit distinct epididymal luminal distribution with segment-specific sperm surface associations', Biology of Reproduction, 99 1022-1033 (2018) [C1]
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2018 |
Xavier MJ, Nixon B, Roman SD, Aitken RJ, 'Improved methods of DNA extraction from human spermatozoa that mitigate experimentally-induced oxidative DNA damage', PLOS ONE, 13 (2018) [C1]
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Nova |
2018 |
Zhou W, Sipilä P, De Iuliis G, Dun MD, Nixon B, 'Analysis of Epididymal Protein Synthesis and Secretion', Jove-Journal of Visualized Experiments, 138 (2018) [C1]
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Nova |
2018 |
Martin J, Bromfield EG, Aitken RJ, Lord T, Nixon B, 'Double Strand Break DNA Repair occurs via Non-Homologous End-Joining in Mouse MII Oocytes', Scientific Reports, 8 1-15 (2018) [C1]
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Nova |
2018 |
Houston BJ, Nixon B, King BV, Aitken RJ, De Iuliis GN, 'Probing the Origins of 1,800 MHz Radio Frequency Electromagnetic Radiation Induced Damage in Mouse Immortalized Germ Cells and Spermatozoa in vitro', FRONTIERS IN PUBLIC HEALTH, 6 (2018) [C1]
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2018 |
Walters JLH, De Iuliis G, Nixon B, Bromfield EG, 'Oxidative Stress in the Male Germline: A Review of Novel Strategies to Reduce 4-Hydroxynonenal Production', Antioxidants, 7 (2018) [C1]
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Nova |
2018 |
Walters JLH, De Iuliis GN, Dun MD, Aitken RJ, McLaughlin EA, Nixon B, Bromfield EG, 'Pharmacological inhibition of arachidonate 15-lipoxygenase protects human spermatozoa against oxidative stress.', Biology of reproduction, 98 784-794 (2018) [C1]
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Nova |
2018 |
Mihalas BP, Bromfield EG, Sutherland JM, De Iuliis GN, McLaughlin EA, John Aitken R, Nixon B, 'Oxidative damage in naturally aged mouse oocytes is exacerbated by dysregulation of proteasomal activity', Journal of Biological Chemistry, 293 18944-18964 (2018) [C1]
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2018 |
Houston BJ, Nixon B, Martin JH, De Iuliis GN, Trigg NA, Bromfield EG, et al., 'Heat exposure induces oxidative stress and DNA damage in the male germ line', BIOLOGY OF REPRODUCTION, 98 593-606 (2018) [C1]
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2017 |
Zhou W, De Iuliis GN, Turner AP, Reid AT, Anderson AL, McCluskey A, et al., 'Developmental expression of the dynamin family of mechanoenzymes in the mouse epididymis', BIOLOGY OF REPRODUCTION, 96 159-173 (2017) [C1]
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2017 |
Bromfield EG, Aitken RJ, McLaughlin EA, Nixon B, 'Proteolytic degradation of heat shock protein A2 occurs in response to oxidative stress in male germ cells of the mouse', MOLECULAR HUMAN REPRODUCTION, 23 91-105 (2017) [C1]
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Nova |
2017 |
Hall SE, Nixon B, Aitken RJ, 'Non-surgical sterilisation methods may offer a sustainable solution to feral horse (Equus caballus) overpopulation', Reproduction, Fertility and Development, 29 1655-1666 (2017) [C1]
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Nova |
2017 |
Katen AL, Sipila P, Mitchell LA, Stanger SJ, Nixon B, Roman SD, 'Epididymal CYP2E1 plays a critical role in acrylamide-induced DNA damage in spermatozoa and paternally mediated embryonic resorptions', BIOLOGY OF REPRODUCTION, 96 921-935 (2017) [C1]
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Nova |
2017 |
Bromfield EG, Mihalas BP, Dun MD, Aitken RJ, McLaughlin EA, Walters JLH, Nixon B, 'Inhibition of arachidonate 15-lipoxygenase prevents 4-hydroxynonenal-induced proteindamage in male germ cells', Biology of Reproduction, 96 598-609 (2017) [C1]
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Nova |
2017 |
Johnston SD, Qualischefski E, Cooper J, McLeod R, Lever J, Nixon B, et al., 'Cryopreservation of saltwater crocodile (Crocodylus porosus) spermatozoa', Reproduction, Fertility and Development, 29 2235-2244 (2017) [C1]
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Nova |
2017 |
Mihalas BP, De Iuliis GN, Redgrove KA, McLaughlin EA, Nixon B, 'The lipid peroxidation product 4-hydroxynonenal contributes to oxidative stress-mediated deterioration of the ageing oocyte', SCIENTIFIC REPORTS, 7 (2017) [C1]
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2017 |
Mihalas BP, Redgrove KA, McLaughlin EA, Nixon B, 'Molecular mechanisms responsible for increased vulnerability of the ageing oocyte to oxidative damage', Oxidative Medicine and Cellular Longevity, 2017 1-22 (2017) [C1]
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Nova |
2017 |
Hutcheon K, McLaughlin EA, Stanger SJ, Bernstein IR, Dun MD, Eamens AL, Nixon B, 'Analysis of the small non-protein-coding RNA profile of mouse spermatozoa reveals specific enrichment of piRNAs within mature spermatozoa', RNA Biology, 14 1776-1790 (2017) [C1]
Post-testicular sperm maturation and storage within the epididymis is a key determinant of gamete quality and fertilization competence. Here we demonstrate that mouse spermatozoa ... [more]
Post-testicular sperm maturation and storage within the epididymis is a key determinant of gamete quality and fertilization competence. Here we demonstrate that mouse spermatozoa possess a complex small non-protein-coding RNA (sRNA) profile, the composition of which is markedly influenced by their epididymal transit. Thus, although microRNAs (miRNAs) are highly represented in the spermatozoa of the proximal epididymis, this sRNA class is largely diminished in mature spermatozoa of the distal epididymis. Coincident with this, a substantial enrichment in Piwi-interacting RNA (piRNA) abundance in cauda spermatozoa was detected. Further, features of cauda piRNAs, including; predominantly 29¿31 nts in length; preference for uracil at their 5' terminus; no adenine enrichment at piRNA nt 10, and; predominantly mapping to intergenic regions of the mouse genome, indicate that these piRNAs are generated by the PIWIL1-directed primary piRNA production pathway. Accordingly, PIWIL1 was detected via immunoblotting and mass spectrometry in epididymal spermatozoa. These data provide insight into the complexity and dynamic nature of the sRNA profile of spermatozoa and raise the intriguing prospect that piRNAs are generated in situ in maturing spermatozoa. Such information is of particular interest in view of the potential role for paternal sRNAs in influencing conception, embryo development and intergenerational inheritance.
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2017 |
Zhou W, Anderson AL, Turner AP, De Iuliis GN, McCluskey A, McLaughlin EA, Nixon B, 'Characterization of a novel role for the dynamin mechanoenzymes in the regulation of human sperm acrosomal exocytosis.', Molecular Human Reproduction, 23 657-673 (2017) [C1]
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2017 |
Martin JH, Bromfield EG, Aitken RJ, Nixon B, 'Biochemical alterations in the oocyte in support of early embryonic development', CELLULAR AND MOLECULAR LIFE SCIENCES, 74 469-485 (2017) [C1]
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2017 |
Hall SE, Aitken RJ, Nixon B, Smith ND, Gibb Z, 'Electrophilic aldehyde products of lipid peroxidation selectively adduct to heat shock protein 90 and arylsulfatase A in stallion spermatozoa', BIOLOGY OF REPRODUCTION, 96 107-121 (2017) [C1]
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2016 |
Redgrove KA, Bernstein IR, Pye VJ, Mihalas BP, Sutherland JM, Nixon B, et al., 'Dynamin 2 is essential for mammalian spermatogenesis', SCIENTIFIC REPORTS, 6 (2016) [C1]
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2016 |
Nixon B, Anderson AL, Smith ND, McLeod R, Johnston SD, 'The Australian saltwater crocodile (Crocodylus porosus) provides evidence that the capacitation of spermatozoa may extend beyond the mammalian lineage', Proceedings of the Royal Society B: Biological Sciences, 283 (2016) [C1]
Although mammalian spermatozoa only acquire functional maturity as they are conveyed through the male (epididymal maturation) and female (capacitation) reproductive tracts, the de... [more]
Although mammalian spermatozoa only acquire functional maturity as they are conveyed through the male (epididymal maturation) and female (capacitation) reproductive tracts, the degree of post-testicular development necessary to achieve fertilization in other vertebrate species remains far less clear. Indeed, despite reports that the epididymis of birds and reptiles is capable of secreting proteins that bind and modify the sperm surface characteristics, it remains unclear whether capacitation is a pre-requisite for fertilization in these species. Using the ancient reptilian Australian saltwater crocodile as a model, this study was undertaken to explore whether reptile sperm do undergo capacitation-like changes following ejaculation. Our studies revealed that crocodile spermatozoa experienced a rapid and sustained, cyclic-AMP mediated increase in progressive motility following incubation under conditions optimized for the induction of capacitation in mammalian species such as the mouse and human. This response was coupled with elevated levels of phosphorylation associated with both protein kinase A and tyrosine kinase substrates, the latter of which were predominantly localized within the sperm flagellum. In findings that also accord with mammalian spermatozoa, we confirmed a homologue of outer dense fibre 2 as one of the principal substrates for tyrosine phosphorylation. Overall, our findings support the concept that crocodile spermatozoa do undergo a process that is homologous to capacitation in preparation for fertilization of an ovum.
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2016 |
Martin JH, Bromfield EG, Aitken RJ, Lord T, Nixon B, 'Data on the concentrations of etoposide, PSC833, BAPTA-AM, and cycloheximide that do not compromise the vitality of mature mouse oocytes, parthenogenetically activated and fertilized embryos', DATA IN BRIEF, 8 1215-1220 (2016)
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2016 |
Houston B, Nixon B, King BV, De Iuliis GN, Aitken RJ, 'The effects of radiofrequency electromagnetic radiation on sperm function', Reproduction, 152 R263-R276 (2016) [C1]
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Nova |
2016 |
Bromfield EG, McLaughlin EA, Aitken RJ, Nixon B, 'Heat shock protein member A2 forms a stable complex with angiotensin convertingenzymeand protein disulfide isomerase A6 in human spermatozoa', Molecular Human Reproduction, 22 93-109 (2016) [C1]
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2016 |
Martin JH, Nixon B, Lord T, Bromfield EG, Aitken RJ, 'Identification of a key role for permeability glycoprotein in enhancing the cellular defense mechanisms of fertilized oocytes', DEVELOPMENTAL BIOLOGY, 417 63-76 (2016) [C1]
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Nova |
2016 |
Nixon B, Ecroyd H, Dacheux J-L, Dacheux F, Labas V, Johnston SD, Jones RC, 'Formation and Dissociation of Sperm Bundles in Monotremes', Biology of Reproduction, 95 1-11 (2016) [C1]
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2016 |
Stanger SJ, Law EA, Jamsai D, O'Bryan MK, Nixon B, McLaughlin EA, et al., 'A novel germ cell protein, SPIF (sperm PKA interacting factor), is essential for the formation of a PKA/TCP11 complex that undergoes conformational and phosphorylation changes upon capacitation', FASEB Journal, 30 2777-2791 (2016) [C1]
Spermatozoa require the process of capacitation to enable them to fertilize an egg. PKA is crucial to capacitation and the development of hyperactivated motility. Sperm PKA is act... [more]
Spermatozoa require the process of capacitation to enable them to fertilize an egg. PKA is crucial to capacitation and the development of hyperactivated motility. Sperm PKA is activated by cAMP generated by the germ cell-enriched adenylyl cyclase encoded by Adcy10. Male mice lacking Adcy10 are sterile, because their spermatozoa are immotile. The current studywas designed to identify binding partners of the sperm-specific (Ca2) catalytic subunit of PKA (PRKACA) by using it as the "bait" in a yeast 2-hybrid system. This approach was used to identify a novel germ cell-enriched protein, sperm PKA interacting factor (SPIF), in 25% of the positive clones. Homozygous Spif-nullmice were embryonically lethal. SPIF was coexpressed and coregulated with PRKACA and with t-complex protein (TCP)-11, a protein associated with PKA signaling. We established that these 3 proteins form part of a novel complex in mouse spermatozoa. Upon capacitation, the SPIF protein becomes tyrosine phosphorylatedin > 95% of sperm. Anapparent molecular rearrangement in the complex occurs, bringing PRKACA and TCP11 into proximity. Taken together, these results suggest a role for the novel complex of SPIF, PRKACA, and TCP11 during spermcapacitation, fertilization, and embryogenesis.
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2016 |
Aitken RJ, Muscio L, Whiting S, Connaughton HS, Fraser BA, Nixon B, et al., 'Analysis of the effects of polyphenols on human spermatozoa reveals unexpected impacts on mitochondrial membrane potential, oxidative stress and DNA integrity; implications for assisted reproductive technology', Biochemical Pharmacology, 121 78-96 (2016) [C1]
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Nova |
2016 |
Reilly JN, McLaughlin EA, Stanger SJ, Anderson AL, Hutcheon K, Church K, et al., 'Characterisation of mouse epididymosomes reveals a complex profile of microRNAs and a potential mechanism for modification of the sperm epigenome', SCIENTIFIC REPORTS, 6 (2016) [C1]
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Nova |
2016 |
Katen AL, Chambers CG, Nixon B, Roman SD, 'Chronic Acrylamide Exposure in Male Mice Results in Elevated DNA Damage in the Germline and Heritable Induction of CYP2E1 in the Testes', BIOLOGY OF REPRODUCTION, 95 (2016) [C1]
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Nova |
2016 |
Katen AL, Stanger SJ, Anderson AL, Nixon B, Roman SD, 'Chronic acrylamide exposure in male mice induces DNA damage to spermatozoa; Potential for amelioration by resveratrol', REPRODUCTIVE TOXICOLOGY, 63 1-12 (2016) [C1]
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2015 |
Anderson AL, Stanger SJ, Mihalas BP, Tyagi S, Holt JE, McLaughlin EA, Nixon B, 'Assessment of microRNA expression in mouse epididymal epithelial cells and spermatozoa by next generation sequencing', Genomics Data, 6 208-211 (2015) [C1]
The mammalian epididymis is a highly specialized region of the male reproductive tract that is lined with a continuous layer of epithelial cells that display a remarkable level of... [more]
The mammalian epididymis is a highly specialized region of the male reproductive tract that is lined with a continuous layer of epithelial cells that display a remarkable level of regionalized secretory and absorptive activity. The luminal environment created by this combined secretory and absorptive activity is directly responsible for promoting the functional maturation of spermatozoa and their maintenance in a quiescent and viable state prior to ejaculation. This study was designed to identify the complement of microRNAs (miRNAs) that are expressed within the mouse epididymal epithelial cells and the maturing populations of spermatozoa. Through the use of Next Generation Sequencing technology we have demonstrated that both epididymal epithelial cells and spermatozoa harbour a complex repertoire of miRNAs that have substantially different expression profiles along the length of the tract. These data, deposited in the Gene Expression Omnibus (GEO) with the accession numbers GSE70197 and GSE70198, afford valuable insight into the post-transcriptional control of gene expression within the epididymis and provide the first evidence for the dynamic transformation of the miRNA content of maturing sperm cells. Ultimately such information promises to inform our understanding of the aetiology of male infertility. Herein we provide a detailed description of the methodology used to generate these important data.
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2015 |
Bromfield E, Aitken RJ, Nixon B, 'Novel characterization of the HSPA2-stabilizing protein BAG6 in human spermatozoa', Molecular Human Reproduction, 21 755-769 (2015) [C1]
While a large cohort of sperm surface receptors underpin sperm-oocyte adhesion processes, our recent work has revealed that the molecular chaperone Heat Shock Protein A2 (HSPA2) i... [more]
While a large cohort of sperm surface receptors underpin sperm-oocyte adhesion processes, our recent work has revealed that the molecular chaperone Heat Shock Protein A2 (HSPA2) is a key regulator of zona pellucida-receptor complex assembly in our own species. Indeed, in the infertile population, spermatozoa that fail to interact with the zona pellucida of the oocyte consistently lack HSPA2 protein expression. While the mechanisms behind this protein deficiency are under consideration, BCL2-associated athanogene 6 (BAG6) has been identified as a key regulator of HSPA2 stability in mouse germ cells. However, in the human, the presence of BAG family proteins remains completely uncharacterized. Consequently, this study aimed to determine the presence of BAG6 in human sperm cells and to characterize its putative interaction with HSPA2 throughout sperm cell development. BAG6 was shown to co-localize with HSPA2 in human testicular germ cells and epididymal spermatozoa. Similarly, BAG6 was identified in the equatorial region of non-capacitated spermatozoa but underwent a marked relocation to the anterior region of the head upon the induction of capacitation in these cells. Protein-protein interaction assays revealed the stable interaction of BAG6 and HSPA2 proteins in mature spermatozoa. Furthermore, examination of the spermatozoa of infertile men with zona pellucida binding defects, related to a lack of HSPA2, revealed a concomitant deficiency in BAG6 protein expression. In view of the findings described in this study, we propose that BAG6 is likely a key regulator of HSPA2 stability/function in human germ cells. Moreover, its under-representation in spermatozoa with zona pellucida binding deficiency suggests that BAG6 may be an important candidate to study for a further understanding of male idiopathic infertility.
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2015 |
Nixon B, Stanger SJ, Mihalas BP, Reilly JN, Anderson AL, Dun MD, et al., 'Next generation sequencing analysis reveals segmental patterns of microRNA expression in mouse epididymal epithelial cells', PLoS ONE, 10 (2015) [C1]
The functional maturation of mammalian spermatozoa is accomplished as the cells descend through the highly specialized microenvironment of the epididymis. This dynamic environment... [more]
The functional maturation of mammalian spermatozoa is accomplished as the cells descend through the highly specialized microenvironment of the epididymis. This dynamic environment is, in turn, created by the combined secretory and absorptive activity of the surrounding epithelium and displays an extraordinary level of regionalization. Although the regulatory network responsible for spatial coordination of epididymal function remains unclear, recent evidence has highlighted a novel role for the RNA interference pathway. Indeed, as noncanonical regulators of gene expression, small noncoding RNAs have emerged as key elements of the circuitry involved in regulating epididymal function and hence sperm maturation. Herein we have employed next generation sequencing technology to profile the genome-wide miRNA signatures of mouse epididymal cells and characterize segmental patterns of expression. An impressive profile of some 370 miRNAs were detected in the mouse epididymis, with a subset of these specifically identified within the epithelial cells that line the tubule (218). A majority of the latter miRNAs (75%) were detected at equivalent levels along the entire length of the mouse epididymis. We did however identify a small cohort of miRNAs that displayed highly regionalized patterns of expression, including miR-204-5p and miR-196b-5p, which were down- and up-regulated by approximately 39- and 45-fold between the caput/caudal regions, respectively. In addition we identified 79 miRNAs (representing ~ 21% of all miRNAs) as displaying conserved expression within all regions of the mouse, rat and human epididymal tissue. These included 8/14 members of let-7 family of miRNAs that have been widely implicated in the control of androgen signaling and the repression of cell proliferation and oncogenic pathways. Overall these data provide novel insights into the sophistication of the miRNA network that regulates the function of the male reproductive tract.
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2015 |
Aitken RJ, Cummins JM, Nixon B, 'The 12 (th) International Symposium on Spermatology.', Asian J Androl, 17 519-520 (2015) [C3]
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2015 |
Aitken RJ, Baker MA, Nixon B, 'Are sperm capacitation and apoptosis the opposite ends of a continuum driven by oxidative stress?', Asian J Androl, 17 633-639 (2015) [C1]
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2015 |
Nixon B, Stanger SJ, Mihalas BP, Reilly JN, Anderson AL, Tyagi S, et al., 'The MicroRNA Signature of Mouse Spermatozoa Is Substantially Modified During Epididymal Maturation', Biology of Reproduction, 93 (2015) [C1]
In recent years considerable effort has been devoted to understanding the epigenetic control of sperm development, leading to an increased appreciation of the importance of RNA in... [more]
In recent years considerable effort has been devoted to understanding the epigenetic control of sperm development, leading to an increased appreciation of the importance of RNA interference pathways, and in particular miRNAs, as key regulators of spermatogenesis and epididymal maturation. It has also been shown that sperm are endowed with an impressive array of miRNA that have been implicated in various aspects of fertilization and embryo development. However, to date there have been no reports on whether the sperm miRNA signature is static or whether it is influenced by their prolonged maturation within the male reproductive tract. To investigate this phenomenon, we employed next-generation sequencing to systematically profile the miRNA signature of maturing mouse spermatozoa. In so doing we have provided the first evidence for the posttesticular modification of the sperm miRNA profile under normal physiological conditions. Such modifications include the apparent loss and acquisition of an impressive cohort of some 113 and 115 miRNAs, respectively, between the proximal and distal epididymal segments. Interestingly, the majority of these changes occur late in maturation and include the uptake of novel miRNA species in addition to a significant increase in many miRNAs natively expressed in immature sperm. Because sperm are not capable of de novo transcription, these findings identify the epididymis as an important site in establishing the sperm epigenome with the potential to influence the peri-conceptual environment of the female reproductive tract, contribute to the inheritance of acquired characteristics, and/or alter the developmental trajectory of the resulting offspring.
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2015 |
Reid AT, Anderson AL, Roman SD, McLaughlin EA, McCluskey A, Robinson PJ, et al., 'Glycogen synthase kinase 3 regulates acrosomal exocytosis in mouse spermatozoa via dynamin phosphorylation', FASEB JOURNAL, 29 2872-2882 (2015) [C1]
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2015 |
Bromfield EG, Aitken RJ, Anderson AL, McLaughlin EA, Nixon B, 'The impact of oxidative stress on chaperone-mediated human sperm-egg interaction.', Hum Reprod, 30 2597-2613 (2015) [C1]
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2015 |
Nixon B, Bromfield EG, Dun MD, Redgrove KA, McLaughlin EA, Aitken RJ, 'The role of the molecular chaperone heat shock protein A2 (HSPA2) in regulating human sperm-egg recognition', ASIAN JOURNAL OF ANDROLOGY, 17 568-573 (2015) [C1]
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2014 |
Nixon BJ, Katen AL, Stanger SJ, Schjenken JE, Nixon B, Roman SD, 'Mouse spermatocytes express CYP2E1 and respond to acrylamide exposure', PLoS ONE, 9 (2014) [C1]
Metabolism of xenobiotics by cytochrome P450s (encoded by the CYP genes) often leads to bio-activation, producing reactive metabolites that interfere with cellular processes and c... [more]
Metabolism of xenobiotics by cytochrome P450s (encoded by the CYP genes) often leads to bio-activation, producing reactive metabolites that interfere with cellular processes and cause DNA damage. In the testes, DNA damage induced by xenobiotics has been associated with impaired spermatogenesis and adverse effects on reproductive health. We previously reported that chronic exposure to the reproductive toxicant, acrylamide, produced high levels of DNA damage in spermatocytes of Swiss mice. CYP2E1 metabolises acrylamide to glycidamide, which, unlike acrylamide, readily forms adducts with DNA. Thus, to investigate the mechanisms of acrylamide toxicity in mouse male germ cells, we examined the expression of the CYP, CYP2E1, which metabolises acrylamide. Using Q-PCR and immunohistochemistry, we establish that CYP2E1 is expressed in germ cells, in particular in spermatocytes. Additionally, CYP2E1 gene expression was upregulated in these cells following in vitro acrylamide exposure (1 µM, 18 h). Spermatocytes were isolated and treated with 1 µM acrylamide or 0.5 µM glycidamide for 18 hours and the presence of DNA-adducts was investigated using the comet assay, modified to detect DNA-adducts. Both compounds produced significant levels of DNA damage in spermatocytes, with a greater response observed following glycidamide exposure. A modified comet assay indicated that direct adduction of DNA by glycidamide was a major source of DNA damage. Oxidative stress played a small role in eliciting this damage, as a relatively modest effect was found in a comet assay modified to detect oxidative adducts following glycidamide exposure, and glutathione levels remained unchanged following treatment with either compound. Our results indicate that the male germ line has the capacity to respond to xenobiotic exposure by inducing detoxifying enzymes, and the DNA damage elicited by acrylamide in male germ cells is likely due to the formation of glycidamide adducts. © 2014 Nixon et al.
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2014 |
Bromfield EG, Aitken RJ, Gibb Z, Lambourne SR, Nixon B, 'Capacitation in the presence of methyl-beta-cyclodextrin results in enhanced zona pellucida-binding ability of stallion spermatozoa', REPRODUCTION, 147 153-166 (2014) [C1]
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2014 |
Nixon B, Ewen KA, Krivanek KM, Clulow J, Kidd G, Ecroyd H, Jones RC, 'Post-testicular sperm maturation and identification of an epididymal protein in the Japanese quail (Coturnix coturnix japonica)', REPRODUCTION, 147 265-277 (2014) [C1]
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2013 |
McIver SC, Roman SD, Nixon B, Loveland KL, McLaughlin EA, 'The rise of testicular germ cell tumours: The search for causes, risk factors and novel therapeutic targets', F1000 Research, 2 1-11 (2013) [C1]
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2013 |
Lord T, Nixon B, Jones KT, Aitken RJ, 'Melatonin Prevents Postovulatory Oocyte Aging in the Mouse and Extends the Window for Optimal Fertilization In Vitro', Biology of Reproduction, 88 1-9 (2013) [C1]
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2013 |
Nixon BJ, Stanger SJ, Nixon B, Roman SD, 'Erratum to Chronic Exposure to Acrylamide Induces DNA Damage in Male Germ Cells of Mice [Toxicological Sciences, 129, 1 (2012) 135-145] doi:10.1093/toxsci/kfs178', Toxicological Sciences, 132 250 (2013)
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2013 |
Redgrove KA, Anderson AL, McLaughlin EA, O'Bryan MK, Aitken RJ, Nixon B, 'Investigation of the mechanisms by which the molecular chaperone HSPA2 regulates the expression of sperm surface receptors involved in human spermoocyte recognition', MOLECULAR HUMAN REPRODUCTION, 19 120-135 (2013) [C1]
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2013 |
Aitken RJ, Nixon B, 'Sperm capacitation: a distant landscape glimpsed but unexplored', Molecular Human Reproduction, 19 785-793 (2013) [C1]
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Nova |
2013 |
Bromfield EG, Nixon B, 'The function of chaperone proteins in the assemblage of protein complexes involved in gamete adhesion and fusion processes', Reproduction, 145 R31-R42 (2013) [C1]
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2013 |
McIver SC, Loveland KL, Roman SD, Nixon B, Kitazawa R, McLaughlin EA, 'The chemokine CXCL12 and its receptor CXCR4 are implicated in human seminoma metastasis', ANDROLOGY, 1 517-529 (2013) [C1]
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2012 |
Reid AT, Lord T, Stanger SJ, Roman SD, McCluskey A, Robinson PJ, et al., 'Dynamin regulates specific membrane fusion events necessary for acrosomal exocytosis in mouse spermatozoa', Journal of Biological Chemistry, 287 37659-37672 (2012) [C1]
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2012 |
Sutherland JM, Keightley RA, Nixon B, Roman SD, Robker RL, Russell DL, McLaughlin EA, 'Suppressor of cytokine signaling 4 (SOCS4): Moderator of ovarian primordial follicle activation', Journal of Cellular Physiology, 227 1188-1198 (2012) [C1]
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2012 |
Sobinoff AP, Pye VJ, Nixon B, Roman SD, McLaughlin EA, 'Jumping the gun: Smoking constituent BaP causes premature primordial follicle activation and impairs oocyte fusibility through oxidative stress', Toxicology and Applied Pharmacology, 260 70-80 (2012) [C1]
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Nova |
2012 |
Dun MD, Anderson AL, Bromfield EG, Asquith KL, Emmett BJ, McLaughlin EA, et al., 'Investigation of the expression and functional significance of the novel mouse sperm protein, a disintegrin and metalloprotease with thrombospondin type 1 motifs number 10 (ADAMTS10)', International Journal of Andrology, 35 572-589 (2012) [C1]
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2012 |
Sobinoff AP, Nixon B, Roman SD, McLaughlin EA, 'Staying alive: PI3K pathway promotes primordial follicle activation and survival in response to 3MC-induced ovotoxicity', Toxicological Sciences, 128 258-271 (2012) [C1]
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Nova |
2012 |
Nixon BJ, Stanger SJ, Nixon B, Roman SD, 'Chronic exposure to acrylamide induces DNA damage in male germ cells of mice', Toxicological Sciences, 129 135-145 (2012) [C1]
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Nova |
2012 |
McIver SC, Roman SD, Nixon B, McLaughlin EA, 'miRNA and mammalian male germ cells', Human Reproduction Update, 18 44-59 (2012) [C1]
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Nova |
2012 |
Dun MD, Aitken RJ, Nixon B, 'The role of molecular chaperones in spermatogenesis and the post-testicular maturation of mammalian spermatozoa', Human Reproduction Update, 18 420-435 (2012) [C1]
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Nova |
2012 |
McIver SC, Stanger SJ, Santarelli DMF, Roman SD, Nixon B, McLaughlin EA, 'A unique combination of male germ cell mirnas coordinates gonocyte differentiation', PLoS One, 7 1-14 (2012) [C1]
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Nova |
2012 |
Redgrove KA, Nixon B, Baker MA, Hetherington L, Baker G, Liu D-Y, Aitken RJ, 'The molecular chaperone HSPA2 plays a key role in regulating the expression of sperm surface receptors that mediate sperm-egg recognition', Plos One, 7 1-16 (2012) [C1]
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2012 |
Baker MA, Nixon B, Naumovski N, Aitken RJ, 'Proteomic insights into the maturation and capacitation of mammalian spermatozoa', Systems Biology in Reproductive Medicine, 58 211-217 (2012) [C1]
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Nova |
2011 |
Redgrove KA, Anderson AL, Dun MD, McLaughlin EA, O'Bryan MK, Aitken RJ, Nixon B, 'Involvement of multimeric protein complexes in mediating the capacitation-dependent binding of human spermatozoa to homologous zonae pellucidae', Developmental Biology, 356 460-474 (2011) [C1]
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2011 |
Dun MD, Smith ND, Baker MA, Lin M, Aitken RJ, Nixon B, 'The chaperonin containing TCP1 complex (CCT/TRiC) is involved in mediating sperm-oocyte interaction', Journal of Biological Chemistry, 286 36875-36887 (2011) [C1]
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2011 |
Nixon B, Mitchell LA, Anderson AL, McLaughlin EA, O'Bryan MK, Aitken RJ, 'Proteomic and functional analysis of human sperm detergent resistant membranes', Journal of Cellular Physiology, 226 2651-2665 (2011) [C1]
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2011 |
Ainsworth CJ, Nixon B, Aitken RJ, 'The electrophoretic separation of spermatozoa: An analysis of genotype, surface carbohydrate composition and potential for capacitation', International Journal of Andrology, 34 e422-e434 (2011) [C1]
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Nova |
2011 |
Nixon B, Ecroyd HW, Dacheux J-L, Jones RC, 'Monotremes provide a key to understanding the evolutionary significance of epididymal sperm maturation', Journal of Andrology, 32 665-671 (2011) [C1]
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Nova |
2011 |
Sobinoff AP, Mahony M, Nixon B, Roman SD, McLaughlin EA, 'Understanding the villain: DMBA-induced preantral ovotoxicity involves selective follicular destruction and primordial follicle activation through PI3K/Akt and mTOR signaling', Toxicological Sciences, 123 563-575 (2011) [C1]
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2010 |
Gibbs GM, Lo JCY, Nixon B, Jamsai D, O'Connor AE, Rijal S, et al., 'Glioma pathogenesis-related 1-Like 1 is testis enriched, dynamically modified, and redistributed during male germ cell maturation and has a potential role in sperm-oocyte binding', Endocrinology, 151 2331-2342 (2010) [C1]
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2010 |
Reid AT, Redgrove KA, Aitken RJ, Nixon B, 'Cellular mechanisms regulating sperm-zona pellucida interaction', Asian Journal of Andrology, 13 88-96 (2010) [C1]
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2010 |
Sobinoff AP, Pye VJ, Nixon B, Roman SD, McLaughlin EA, 'Adding insult to injury: Effects of xenobiotic-induced preantral ovotoxicity on ovarian development and oocyte fusibility', Toxicological Sciences, 118 653-666 (2010) [C1]
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2010 |
Nixon B, Bielanowicz AJ, Anderson AL, Walsh AK, Hall TE, McCloghry AK, Aitken RJ, 'Elucidation of the signaling pathways that underpin capacitation-associated surface phosphotyrosine expression in mouse spermatozoa', Journal of Cellular Physiology, 224 71-83 (2010) [C1]
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2009 |
Bennetts LE, De Iuliis GN, Nixon B, Kime M, Zelski K, McVicar CM, et al., 'Impact of Estrogenic Compounds on DNA Integrity in Human Spermatozoa: Evidence for Cross-Linking and Redox Cycling Activities', JOURNAL OF UROLOGY, 181 914-915 (2009) [C1]
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2009 |
De Iuliis GN, Thomson LK, Mitchell LA, Read JM, Koppers AJ, Hedges A, et al., 'DNA damage in human spermatozoa is highly correlated with the efficiency of chromatin remodeling and the formation of 8-hydroxy-2'-deoxyguanosine, a marker of oxidative stress', Biology of Reproduction, 81 517-524 (2009) [C1]
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Nova |
2009 |
Nixon B, Bielanowicz AJ, McLaughlin EA, Tanphaichitr N, Ensslin MA, Aitken RJ, 'Composition and significance of detergent resistant membranes in mouse spermatozoa', Journal of Cellular Physiology, 218 122-134 (2009) [C1]
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Nova |
2009 |
Nixon B, Aitken RJ, 'The biological significance of detergent-resistant membranes in spermatozoa', Journal of Reproductive Immunology, 83 8-13 (2009) [C1]
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Nova |
2009 |
Dacheux J-L, Dacheux F, Labas V, Ecroyd H, Nixon B, Jones RC, 'New proteins identified in epididymal fluid from the platypus (Ornithorhynchus anatinus)', Reproduction Fertility and Development, 21 1002-1007 (2009) [C1]
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2009 |
Ecroyd H, Nixon B, Dacheux J-L, Jones RC, 'Testicular descent, sperm maturation and capacitation: Lessons from our most distant relatives, the monotremes', Reproduction Fertility and Development, 21 992-1001 (2009) [C1]
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2008 |
Mitchell LA, Nixon B, Baker MA, Aitken RJ, 'Investigation of the role of SRC in capacitation-associated tyrosine phosphorylation of human spermatozoa', Molecular Human Reproduction, 14 235-243 (2008) [C1]
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Nova |
2008 |
Grutzner F, Nixon B, Jones RC, 'Reproductive biology in egg-laying mammals', Sexual Development, 2 115-127 (2008) [C1]
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Nova |
2008 |
Nixon B, Jones RC, Holland MK, 'Molecular and functional characterization of the rabbit epididymal secretory protein 52, REP52', Biology of Reproduction, 78 910-920 (2008) [C1]
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Nova |
2008 |
Walsh AK, Whelan D, Bielanowicz AJ, Skinner BL, Aitken RJ, O'Bryan MK, Nixon B, 'Identification of the molecular chaperone, heat shock protein 1 (chaperonin 10), in the reproductive tract and in capacitating spermatozoa in the male mouse', Biology of Reproduction, 78 983-993 (2008) [C1]
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Nova |
2008 |
Warren WC, Hillier LW, Graves JAM, Birney E, Ponting CP, Grutzner F, et al., 'Genome analysis of the platypus reveals unique signatures of evolution (vol 453, pg 175, 2008)', NATURE, 455 256-256 (2008) [C3]
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2008 |
Warren WC, Hillier LW, Graves JAM, Birney E, Ponting CP, Grutzner F, et al., 'Genome analysis of the platypus reveals unique signatures of evolution', Nature, 453 175-U1 (2008) [C1]
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Nova |
2008 |
Priestley MN, Dunstan RH, O'Connor WA, Van Zwieten L, Nixon B, Macfarlane GR, 'Effects of 4-nonylphenol and 17 alpha-ethynylestradiol exposure in the Sydney rock oyster, Saccostrea glomerata: Vitellogenin induction and gonadal development', Aquatic Toxicology, 88 39-47 (2008) [C1]
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2007 |
Aitken RJ, Nixon B, Lin M, Koppers AJ, Lee YH, Baker MA, 'Proteomic changes in mammalian spermatozoa during epididymal maturation', Asian Journal of Andrology, 9 554-564 (2007) [C1]
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2007 |
Jones RC, Dacheux JL, Nixon B, Ecroyd HW, 'Role of the epididymis in sperm competition', Asian Journal of Andrology, 9 493-499 (2007) [C1]
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2007 |
Mitchell LA, Nixon B, Aitken RJ, 'Analysis of chaperone proteins associated with human spermatozoa during capacitation', Molecular Human Reproduction, 13 605-613 (2007) [C1]
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2007 |
Nixon B, Aitken RJ, McLaughlin EA, 'New insights into the molecular mechanisms of sperm-egg interaction', Cellular and Molecular Life Sciences, 64 1805-1823 (2007) [C1]
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2007 |
Ainsworth CJ, Nixon B, Jansen RPS, Aitken RJ, 'First recorded pregnancy and normal birth after ICSI using electrophoretically isolated spermatozoa', Human Reproduction, 22 197-200 (2007) [C1]
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2006 |
Nixon B, Macintyre DA, Mitchell LA, Gibbs GM, O'Bryan M, Aitken RJ, 'The identification of mouse sperm-surface-associated proteins and characterization of their ability to act as decapacitation factors', Biology of Reproduction, 74 275-287 (2006) [C1]
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Nova |
2005 |
Nixon B, Paul JW, Spiller CM, Attwell-Heap AG, Ashman LK, Aitken RJ, 'Evidence for the involvement of PECAM-1 in a receptor mediated signal-transduction pathway regulating capacitation-associated tyrosine phosphorylation in human spermatozoa', Journal of Cell Science, 118 4865-4877 (2005) [C1]
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Nova |
2005 |
Nixon B, Asquith KL, Aitken RJ, 'The role of molecular chaperones in mouse sperm-egg interactions', Molecular and Cellular Endocrinology, 240 1-10 (2005) [C1]
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Nova |
2005 |
Ainsworth CJ, Nixon B, Aitken RJ, 'Development of a novel electrophoretic system for the isolation of human spermatozoa', Human Reproduction, 20 2261-2270 (2005) [C1]
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Nova |
2005 |
Asquith KL, Bielanowicz AJ, McLaughlin EA, Nixon B, Aitken RJ, 'Localization and significance of molecular chaperones, heat shock protein 1, and tumor rejection antigen gp96 in the male reproductive tract and during capacitation and acrosome reaction', Biology of Reproduction, 72 328-337 (2005) [C1]
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Nova |
2004 |
Asquith KL, Baleato R, McLaughlin EA, Nixon B, Aitken RJ, 'Tyrosine phosphorylation activates surface chaperones facilitating sperm-zona recognition', Journal of Cell Science, 117 3645-3657 (2004) [C1]
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Nova |
2004 |
Curry BJ, Su H, Law EG, McLaughlin EA, Nixon B, Aitken RJ, 'Identification of RARhoGAP, a novel putative RhoGAP gene expressed in male germ cells', Genomics, 84 406-418 (2004) [C1]
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2002 |
Nixon B, Jones RC, Hansen LA, Holland M, 'Rabbit epididymal secretory proteins. I. Characterization and hormonal regulation', Biology of Reproduction, 67 133-139 (2002) [C1]
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2002 |
Nixon B, Jones RC, Clarke H, Holland M, 'Rabbit epididymal secretory proteins. II. Immunolocalization and sperm association of REP38', Biology of Reproduction, 67 140-146 (2002) [C1]
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2002 |
Nixon B, Hardy C, Jones RC, Anfrews J, Holland M, 'Rabbit epididymal secretory proteins. III. Molecular cloning and characterization of the complementary DNA for REP38', Biology of Reproduction, 67 147-153 (2002) [C1]
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2001 |
Nixon B, Lu QX, Wassler MJ, Foote CI, Ensslin MA, Shur BD, 'Galactosyltransferase function during mammalian fertilization', CELLS TISSUES ORGANS, 168 46-57 (2001) [C1]
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1998 |
Holland MK, Nixon B, 'The specificity of epididymal secretory proteins', Journal of Reproduction and Fertility, 197-210 (1998) |
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1997 |
Hardy C, Clarke H, Nixon B, Hinds L, Holland M, 'Examination of the immunocontraceptive potential of recombinant fertilin subunits in rabbits', Biology of Reproduction, 57 879-886 (1997) [C1]
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