2023 |
Grace T, Fisher J, Wang C, Valkenborghs SR, Smith R, Hirst JJ, et al., 'Newcastle 1000 (NEW1000) Study: an Australian population-based prospective pregnancy cohort study design and protocol', BMJ OPEN, 13 (2023)
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2023 |
Moloney RA, Pavy CL, Kahl RGS, Palliser HK, Hirst JJ, Shaw JC, 'Dual isolation of primary neurons and oligodendrocytes from guinea pig frontal cortex.', Front Cell Neurosci, 17 1298685 (2023) [C1]
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Nova |
2023 |
Crombie GK, Palliser HK, Shaw JC, Hanley BA, Moloney RA, Hirst JJ, 'Prenatal Stress Induces Translational Disruption Associated with Myelination Deficits.', Developmental neuroscience, 45 290-308 (2023) [C1]
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Nova |
2023 |
Ajgaonkar S, Hirst JJ, Norris M, Zakar T, 'Regulation of inflammatory genes in decidual cells: Involvement of the bromodomain and extra-terminal family proteins', PLoS ONE, 18 (2023) [C1]
The decidua undergoes proinflammatory activation in late pregnancy, promoting labor. Bromodomain and Extra-Terminal (BET) family proteins interact with acetylated histones and may... [more]
The decidua undergoes proinflammatory activation in late pregnancy, promoting labor. Bromodomain and Extra-Terminal (BET) family proteins interact with acetylated histones and may control gene expression in inflammation. Here, we assessed whether BETs are involved in inflammatory gene regulation in human decidual cells. We have treated primary cultures of decidual stromal cells (DSCs) from term pregnancies with endotoxin (LPS) and measured the expression of a panel of pro-and anti-inflammatory genes. BET involvement was assessed using the selective BET inhibitors (+)-JQ1 and I-BET-762 or the negative control compound (-)-JQ1. Histone 3 and -4 acetylation and BETs binding at the target gene promoters were determined to assess whether these processes are involved in the actions of LPS, BETs, and BET inhibitors. LPS increased the expression of the proinflammatory (PTGS2, IL6, CXCL8/IL8, TNF) and the anti-inflammatory (IL10, IDO1) genes of the panel. The constitutively expressed inflammatory genes (PTGS1, PTGES) were unaffected. The BET inhibitors, but not the control compound, reduced the basal and LPS-induced expression of PTGS1, PTGS2, IL6, CXCL8/IL8, IL10, and IDO1. TNF expression was not changed by BET inhibition. The dominant BETs were Bromodomain-containing protein -2 (BRD2) and -4L (BRD4L) in DSCs. LPS increased histone 4 acetylation at the CXCL8/IL8 and TNF promoters and histone 3 and -4 acetylation at the IDO1 promoter, while (+)-JQ1 abrogated histone acetylation at several promoters. Overall, histone acetylation and promoter binding of BETs showed no consistent relationship with gene expression across the gene panel and the treatments. BET proteins, predominantly BRD2 and BRD4L, control critical pro- and anti-inflammatory genes in DSCs. TNF induction exemplifies a BET-independent pathway. Changing histone acetylation at the promoters is not a general obligatory requirement for inflammatory gene expression in response to LPS. BETs likely act at chromatin loci separate from the examined promoters. BET inhibitors may block decidual activation at labor.
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2022 |
Crombie GK, Palliser HK, Shaw JC, Hodgson DM, Walker DW, Hirst JJ, 'Evaluating changes in GABAergic and glutamatergic pathways in early life following prenatal stress and postnatal neurosteroid supplementation', PSYCHONEUROENDOCRINOLOGY, 139 (2022) [C1]
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Nova |
2022 |
Shaw JC, Dyson RM, Palliser HK, Sixtus RP, Barnes H, Pavy CL, et al., 'Examining Neurosteroid-Analogue Therapy in the Preterm Neonate For Promoting Hippocampal Neurodevelopment', FRONTIERS IN PHYSIOLOGY, 13 (2022) [C1]
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Nova |
2022 |
Shaw JC, Dyson RM, Palliser HK, Crombie GK, Berry MJ, Hirst JJ, 'Adaptations in the Hippocampus during the Fetal to Neonatal Transition in Guinea Pigs', Reproductive Medicine, 3 85-100 [C1]
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2022 |
Miller SL, Bennet L, Sutherland AE, Pham Y, McDonald C, Castillo-Melendez M, et al., 'Ganaxolone versus Phenobarbital for Neonatal Seizure Management', ANNALS OF NEUROLOGY, 92 1066-1079 (2022) [C1]
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Nova |
2021 |
Crombie GK, Palliser HK, Shaw JC, Hodgson DM, Walker DW, Hirst JJ, 'Effects of prenatal stress on behavioural and neurodevelopmental outcomes are altered by maternal separation in the neonatal period', PSYCHONEUROENDOCRINOLOGY, 124 (2021) [C1]
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Nova |
2021 |
Crombie GK, Palliser HK, Shaw JC, Hodgson DM, Walker DW, Hirst JJ, 'Neurosteroid-based intervention using Ganaxolone and Emapunil for improving stress-induced myelination deficits and neurobehavioural disorders', PSYCHONEUROENDOCRINOLOGY, 133 (2021) [C1]
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Nova |
2021 |
Cumberland AL, Hirst JJ, Badoer E, Wudy SA, Greaves RF, Zacharin M, Walker DW, 'The enigma of the adrenarche: Identifying the early life mechanisms and possible role in postnatal brain development', International Journal of Molecular Sciences, 22 (2021) [C1]
Dehydroepiandrosterone (DHEA) and its sulfated metabolite (DHEAS) are dynamically regulated before birth and the onset of puberty. Yet, the origins and purpose of increasing DHEA[... [more]
Dehydroepiandrosterone (DHEA) and its sulfated metabolite (DHEAS) are dynamically regulated before birth and the onset of puberty. Yet, the origins and purpose of increasing DHEA[S] in postnatal development remain elusive. Here, we draw attention to this pre-pubertal surge from the adrenal gland¿the adrenarche¿and discuss whether this is the result of intra-adrenal gene expression specifically affecting the zona reticularis (ZR), if the ZR is influenced by the hypothalamic-pituitary axis, and the possible role of spino-sympathetic innervation in prompting increased ZR activity. We also discuss whether neural DHEA[S] synthesis is coordinately regulated with the developing adrenal gland. We propose that DHEA[S] is crucial in the brain maturation of humans prior to and during puberty, and suggest that the function of the adrenarche is to modulate, adapt and rewire the pre-adolescent brain for new and ever-changing social challenges. The etiology of DHEA[S] synthesis, neurodevelopment and recently described 11-keto and 11-oxygenated androgens are difficult to investigate in humans owing to: (i) ethical restrictions on mechanistic studies, (ii) the inability to predict which individuals will develop specific mental characteristics, and (iii) the difficulty of conducting retrospective studies based on perinatal complications. We discuss new opportunities for animal studies to overcome these important issues.
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Nova |
2021 |
Shaw JC, Crombie GK, Palliser HK, Hirst JJ, 'Impaired Oligodendrocyte Development Following Preterm Birth: Promoting GABAergic Action to Improve Outcomes', FRONTIERS IN PEDIATRICS, 9 (2021) [C1]
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Nova |
2019 |
Shaw JC, Crombie GK, Zakar T, Palliser HK, Hirst JJ, 'Perinatal compromise contributes to programming of GABAergic and glutamatergic systems leading to long-term effects on offspring behaviour', JOURNAL OF NEUROENDOCRINOLOGY, 32 (2019) [C1]
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Nova |
2019 |
Shaw JC, Berry MJ, Dyson RM, Crombie GK, Hirst JJ, Palliser HK, 'Reduced Neurosteroid Exposure Following Preterm Birth and Its' Contribution to Neurological Impairment: A Novel Avenue for Preventative Therapies', Frontiers in Physiology, 10 (2019) [C1]
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Nova |
2019 |
Mitchell CM, Hirst JJ, Mitchell MD, Murray HG, Zakar T, 'Genes upregulated in the amnion at labour are bivalently marked by activating and repressive histone modifications', Molecular Human Reproduction, 25 228-240 (2019) [C1]
Inflammatory genes are expressed increasingly in the foetal membranes at late gestation triggering birth. Here we have examined whether epigenetic histone modifications contribute... [more]
Inflammatory genes are expressed increasingly in the foetal membranes at late gestation triggering birth. Here we have examined whether epigenetic histone modifications contribute to the upregulation of proinflammatory genes in the amnion in late pregnancy and at labour. Amnion samples were collected from early pregnancy, at term in the absence of labour and after spontaneous birth. The expression of the labour-Associated proinflammatory genes PTGS2, BMP2 and NAMPT was determined by reverse transcription-coupled quantitative real-Time PCR (qRT-PCR). Chromatin immunoprecipitation (ChIP) and sequential double ChIP were performed to determine the levels and co-occurrence of activating histone-3, lysine-4 trimethylation (H3K4me3) and repressive histone-3, lysine-27 trimethylation (H3K27me3) at the gene promoters. H3K4 methyltransferase, H3K27me3 demethylase and H3K27 methyltransferase expression was determined by qRT-PCR and immunofluorescence confocal microscopy. PTGS2, BMP2 and NAMPT expression was upregulated robustly between early pregnancy and term (P < 0.05). The promoters were marked bivalently by both the H3K4me3 and H3K27me3 modifications. Bivalence was reduced at term by the decrease of the H3K27me3-modified fraction of promoter copies marked by H3K4me3 indicating epigenetic activation. Messenger RNAs encoding the H3K4-specific methyl transferases MLL1,-2,-3,-4, SETD1A,-B and the H3K27me3-specific demethylases KDM6A,-B were expressed increasingly while the H3K27 methyl transferase EZH2 was expressed decreasingly at term. Histone modifying enzyme proteins were detected in amnion epithelial and mesenchymal cells. These results with prototypical proinflammatory genes suggest that nucleosomes at labour-promoting genes are marked bivalently in the amnion, which is shifted towards monovalent H3K4me3 modification at term when the genes are upregulated. Bivalent epigenetic regulation by histone modifying enzymes may control the timing of labour.
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Nova |
2019 |
Shaw JC, Dyson RM, Palliser HK, Gray C, Berry MJ, Hirst JJ, 'Neurosteroid replacement therapy using the allopregnanolone-analogue ganaxolone following preterm birth in male guinea pigs', Pediatric Research, 85 86-96 (2019) [C1]
Background: Children born preterm, especially boys, are at increased risk of developing attention deficit hyperactivity disorder (ADHD) and learning difficulties. We propose that ... [more]
Background: Children born preterm, especially boys, are at increased risk of developing attention deficit hyperactivity disorder (ADHD) and learning difficulties. We propose that neurosteroid-replacement therapy with ganaxolone (GNX) following preterm birth may mitigate preterm-associated neurodevelopmental impairment. Methods: Time-mated sows were delivered preterm (d62) or at term (d69). Male preterm pups were randomized to ganaxolone (Prem-GNX; 2.5 mg/kg subcutaneously twice daily until term equivalence), or preterm control (Prem-CON). Surviving male juvenile pups underwent behavioural testing at d25-corrected postnatal age (CPNA). Brain tissue was collected at CPNA28 and mature myelinating oligodendrocytes of the hippocampus and subcortical white matter were quantified by immunostaining of myelin basic protein (MBP). Results: Ganaxolone treatment returned the hyperactive behavioural phenotype of preterm-born juvenile males to a term-born phenotype. Deficits in MBP immunostaining of the preterm hippocampus and subcortical white matter were also ameliorated in animals receiving ganaxolone. However, during the treatment period weight gain was poor, and pups were sedated, ultimately increasing the neonatal mortality rate. Conclusion: Ganaxolone improved neurobehavioural outcomes in males suggesting that neonatal treatment may be an option for reducing preterm-associated neurodevelopmental impairment. However, dosing studies are required to reduce the burden of unwanted side effects.
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Nova |
2019 |
Greaves RF, Wudy SA, Badoer E, Zacharin M, Hirst JJ, Quinn T, Walker DW, 'A tale of two steroids: The importance of the androgens DHEA and DHEAS for early neurodevelopment', Journal of Steroid Biochemistry and Molecular Biology, 188 77-85 (2019) [C1]
DHEA and DHEAS are neuroactive neurosteroids that interact with several major receptor systems in the brain, including sigma (s), glutamate, and GABA-A receptors. It has been reco... [more]
DHEA and DHEAS are neuroactive neurosteroids that interact with several major receptor systems in the brain, including sigma (s), glutamate, and GABA-A receptors. It has been recognized as early as 1952, that the loss of DHEA/DHEAS in adult life is associated with neuropsychiatric disorders (eg schizophrenia, depression). However, the mechanistic role for DHEA/DHEAS in any of these domains remains speculative, not the least because the presence of these androgens in the adrenal gland and brain is largely confined to humans and only some non-human primates. DHEA and DHEAS are dynamically regulated from before birth and before the onset of puberty, and therefore an understanding of the synthesis, regulation, and functions of this important androgen pathway warrants attention. Here, we draw attention to the possible modulating influence of DHEA/DHEAS in early brain development from fetal life to the remarkable increase of these steroids in early childhood - the adrenarche. We propose that the pre-pubertal DHEA/DHEAS surge plays a key role in modulating early brain development, perhaps by prolonging brain plasticity during childhood to allow the pre-adolescent brain to adapt and re-wire in response to new, and ever-changing social challenges. Nonetheless, the aetiology of neurodevelopmental phenomena in relation to DHEA/DHEAS synthesis and action cannot be easily studied in humans due to the obvious ethical restrictions on mechanistic studies, the uncertainty of predicting the future mental characteristics of individuals, and the difficulty of conducting retrospective investigations based on pre-birth and/or neonatal complications. We discuss new opportunities for animal studies to resolve these important questions.
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Nova |
2018 |
Hirst JJ, Palliser HK, Shaw JC, Crombie G, Walker DW, Zakar T, 'Birth and Neonatal Transition in the Guinea Pig: Experimental Approaches to Prevent Preterm Birth and Protect the Premature Fetus', FRONTIERS IN PHYSIOLOGY, 9 (2018) [C1]
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Nova |
2018 |
Shaw JC, Palliser HK, Dyson RM, Berry MJ, Hirst JJ, 'Disruptions to the cerebellar GABAergic system in juvenile guinea pigs following preterm birth', International Journal of Developmental Neuroscience, 65 1-10 (2018) [C1]
Background Children that are born preterm are at an increased risk of developing cognitive problems and behavioural disorders, such as attention deficit hyperactivity disorder (AD... [more]
Background Children that are born preterm are at an increased risk of developing cognitive problems and behavioural disorders, such as attention deficit hyperactivity disorder (ADHD). There is increasing interest in the role of the cerebellum in these processes and the potential involvement of GABAergic pathways in neurodevelopmental disorders. We propose that preterm birth, and the associated loss of the trophic intrauterine environment, alters the development of the cerebellum, contributing to ongoing neurobehavioral disorders. Methods Guinea pigs were delivered preterm (GA62) or spontaneously at term (GA69), and tissues collected at corrected postnatal day (PND) 28. Neurodevelopmental and GABAergic markers myelin basic protein (MBP), neuronal nuclei (NeuN), calbindin (Purkinje cells), and GAD67 (GABA synthesis enzyme) were analysed in cerebellar lobules IX and X by immunohistochemistry. Protein expression of GAD67 and GAT1 (GABA transporter enzyme) were quantified by western blot, whilst neurosteroid-sensitive GABAA receptor subunits were measured by RT-PCR. Results MBP immunostaining was increased in lobule IX of preterm males, and reduced in lobule X of preterm females when compared to their term counterparts. GAD67 staining was decreased in lobule IX and X of the preterm males, but only in lobule X of the preterm females compared to term cohorts for each sex. Internal granule cell layer width of lobule X was decreased in preterm cohorts of both sexes compared to terms. There were no differences between gestational age groups for NeuN staining, GAD67 and GAT1 protein expression as measured by western blotting, or GABAA receptor subunits as measured by RT-PCR between preterm and term for either sex. Conclusions The present findings suggest that components of the cerebellar GABAergic system of the ex-preterm cerebellum are disrupted. The higher expression of myelin in the preterm males may be due to a deficit in axonal pruning, whereas females have a deficit in myelination at 28 corrected days of age. Together these ongoing alterations may contribute to the neurodevelopmental and behavioural disorders observed in those born preterm.
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Nova |
2018 |
Shaw JC, Palliser HK, Palazzi K, Hirst JJ, 'Administration of Progesterone Throughout Pregnancy Increases Maternal Steroids Without Adverse Effect on Mature Oligodendrocyte Immunostaining in the Guinea Pig', Reproductive Sciences, 25 395-405 (2018) [C1]
Progesterone is administered to pregnant women at risk of premature labor, despite systematic reviews showing conflicting outcomes regarding its use, highlighting doubt over the e... [more]
Progesterone is administered to pregnant women at risk of premature labor, despite systematic reviews showing conflicting outcomes regarding its use, highlighting doubt over the effectiveness of the therapy. Progesterone can be rapidly metabolized into a number of steroids, but to date, there has been a lack of investigation into the fetal steroid profiles following administration and whether this impacts fetal neurodevelopment. The objective of this study was to determine the effect of progesterone treatment on allopregnanolone and cortisol levels in the fetus and on a marker of myelination in the fetal brain. We used a guinea pig model where pregnant dams were administered vehicle (ß-cyclodextrin) or progesterone orally throughout pregnancy (GA29-61). Maternal and fetal fluids and tissues were collected at both preterm (GA61) and term (GA68) ages. Maternal and fetal progesterone and cortisol were analyzed by enzyme immunoassay and allopregnanolone by radioimmunoassay. Measurement of myelination of fetal brains (hippocampus, cingulum, and subcortical white matter) at preterm and term ages was performed by immunohistochemistry staining for myelin basic protein. We found that dams receiving progesterone had significantly elevated progesterone and cortisol concentrations, but there was no effect on allopregnanolone. Interestingly, the increased cortisol concentrations were not reflected in the fetuses, and there was no effect of progesterone treatment on myelination. Therefore, we conclude that in our guinea pig model, maternal administration of progesterone has no effect on cortisol levels or markers of mature oligodendrocytes in the fetus and suggest this is potentially due to the protective cortisol barrier in the placenta.
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Nova |
2018 |
Ellery SJ, Kelleher M, Grigsby P, Burd I, Derks JB, Hirst J, et al., 'Antenatal prevention of cerebral palsy and childhood disability: is the impossible possible?', Journal of Physiology, 596 5593-5609 (2018) [C1]
This review covers our current knowledge of the causes of perinatal brain injury leading to cerebral palsy-like outcomes, and argues that much of this brain damage is preventable.... [more]
This review covers our current knowledge of the causes of perinatal brain injury leading to cerebral palsy-like outcomes, and argues that much of this brain damage is preventable. We review the experimental evidence that there are treatments that can be safely administered to women in late pregnancy that decrease the likelihood and extent of perinatal brain damage that occurs because of acute and severe hypoxia that arises during some births, and the additional impact of chronic fetal hypoxia, infection, inflammation, growth restriction and preterm birth. We discuss the types of interventions required to ameliorate or even prevent apoptotic and necrotic cell death, and the vulnerability of all the major cell types in the brain (neurons, astrocytes, oligodendrocytes, microglia, cerebral vasculature) to hypoxia/ischaemia, and whether a pan-protective treatment given to the mother before birth is a realistic prospect. (Figure presented.).
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Nova |
2018 |
Morrison JL, Botting KJ, Darby JRT, David AL, Dyson RM, Gatford KL, et al., 'Guinea pig models for translation of the developmental origins of health and disease hypothesis into the clinic', Journal of Physiology, 596 5535-5569 (2018) [C1]
Over 30¿years ago Professor David Barker first proposed the theory that events in early life could explain an individual's risk of non-communicable disease in later life: the... [more]
Over 30¿years ago Professor David Barker first proposed the theory that events in early life could explain an individual's risk of non-communicable disease in later life: the developmental origins of health and disease (DOHaD) hypothesis. During the 1990s the validity of the DOHaD hypothesis was extensively tested in a number of human populations and the mechanisms underpinning it characterised in a range of experimental animal models. Over the past decade, researchers have sought to use this mechanistic understanding of DOHaD to develop therapeutic interventions during pregnancy and early life to improve adult health. A variety of animal models have been used to develop and evaluate interventions, each with strengths and limitations. It is becoming apparent that effective translational research requires that the animal paradigm selected mirrors the tempo of human fetal growth and development as closely as possible so that the effect of a perinatal insult and/or therapeutic intervention can be fully assessed. The guinea pig is one such animal model that over the past two decades has demonstrated itself to be a very useful platform for these important reproductive studies. This review highlights similarities in the in utero development between humans and guinea pigs, the strengths and limitations of the guinea pig as an experimental model of DOHaD and the guinea pig's potential to enhance clinical therapeutic innovation to improve human health. (Figure presented.).
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Nova |
2017 |
Cumberland AL, Palliser HK, Crombie GK, Walker DW, Hirst JJ, 'Increased anxiety-like phenotype in female guinea pigs following reduced neurosteroid exposure in utero', International Journal of Developmental Neuroscience, 58 50-58 (2017) [C1]
Neurosteroids are essential for aiding proper fetal neurodevelopment. Pregnancy compromises such as preterm birth, prenatal stress and intrauterine growth restriction are associat... [more]
Neurosteroids are essential for aiding proper fetal neurodevelopment. Pregnancy compromises such as preterm birth, prenatal stress and intrauterine growth restriction are associated with an increased risk of developing behavioural and mood disorders, particularly during adolescence. These pathologies involve the premature loss or alteration of trophic steroid hormones reaching the fetus leading to impaired neurodevelopment. While the specific programming mechanisms are yet to be fully elucidated, in adult life, dysfunctions of allopregnanolone action are prevalent in individuals with depression, post-traumatic stress disorder and anxiety disorders. The objective of this study was to assess if changes in concentrations of the neurosteroid, allopregnanolone, may be a fetal programming factor in priming the brain towards a negative behavioural phenotype during the childhood to adolescent period using a guinea pig model. Pregnant guinea pigs received either vehicle (45% (2-hydroxypropyl)-ß-cyclodextrin) or the 5a-reductase inhibitor, finasteride (25¿mg/kg maternal weight) from gestational age 60 until spontaneous delivery (~71¿days gestation). Male and female offspring from vehicle and finasteride treated dams were tested at postnatal day 20 (juvenile-equivalence) in an open field arena, and hippocampus and amygdala subsequently assessed for neurological changes in markers of development and GABA production pathways 24¿h later. Females with reduced allopregnanolone exposure in utero displayed increased neophobic-like responses to a change in their environment compared to female controls. There were no differences in the neurodevelopmental markers assessed; MAP2, NeuN, MBP, GFAP or GAD67 between intrauterine finasteride or vehicle exposure, in either the hippocampus or amygdala whereas GAT1 staining was decreased. This study indicates that an intrauterine reduction in the supply of allopregnanolone programs vulnerability of female offspring to anxiety-like disorders in juvenility without impacting long term allopregnanolone concentrations.
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Nova |
2017 |
Cumberland AL, Palliser HK, Rani P, Walker DW, Hirst JJ, 'Effects of combined IUGR and prenatal stress on the development of the hippocampus in a fetal guinea pig model.', J Dev Orig Health Dis, 8 584-596 (2017) [C1]
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Nova |
2017 |
Bennett GA, Palliser HK, Shaw JC, Palazzi KL, Walker DW, Hirst JJ, 'Maternal stress in pregnancy affects myelination and neurosteroid regulatory pathways in the guinea pig cerebellum', Stress, 20 580-588 (2017) [C1]
Prenatal stress predisposes offspring to behavioral pathologies. These may be attributed to effects on cerebellar neurosteroids and GABAergic inhibitory signaling, which can be li... [more]
Prenatal stress predisposes offspring to behavioral pathologies. These may be attributed to effects on cerebellar neurosteroids and GABAergic inhibitory signaling, which can be linked to hyperactivity disorders. The aims were to determine the effect of prenatal stress on markers of cerebellar development, a key enzyme in neurosteroid synthesis and the expression of GABAA receptor (GABAAR) subunits involved in neurosteroid signaling. We used a model of prenatal stress (strobe light exposure, 2 h on gestational day 50, 55, 60 and 65) in guinea pigs, in which we have characterized anxiety and neophobic behavioral outcomes. The cerebellum and plasma were collected from control and prenatally stressed offspring at term (control fetus: n = 9 male, n = 7 female; stressed fetus: n = 7 male, n = 8 female) and postnatal day (PND) 21 (control: n = 8 male, n = 8 female; stressed: n = 9 male, n = 6 female). We found that term female offspring exposed to prenatal stress showed decreased expression of mature oligodendrocytes (~40% reduction) and these deficits improved to control levels by PND21. Reactive astrocyte expression was lower (~40% reduction) following prenatal stress. GABAAR subunit (d and a6) expression and circulating allopregnanolone concentrations were not affected by prenatal stress. Prenatal stress increased expression (~150¿250% increase) of 5a-reductase type-1 mRNA in the cerebellum, which may be a neuroprotective response to promote GABAergic inhibition and aid in repair. These observations indicate that prenatal stress exposure has marked effects on the development of the cerebellum. These findings suggest cerebellar changes after prenatal stress may contribute to adverse behavioral outcomes after exposure to these stresses.
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Nova |
2017 |
Cumberland AL, Palliser HK, Walker DW, Hirst JJ, 'Cerebellar Changes in Guinea Pig Offspring Following Suppression of Neurosteroid Synthesis During Late Gestation', Cerebellum, 16 306-313 (2017) [C1]
Elevated gestational concentrations of allopregnanolone are essential for the development and neuroprotection of the foetal brain. Preterm birth deprives the foetus of these high ... [more]
Elevated gestational concentrations of allopregnanolone are essential for the development and neuroprotection of the foetal brain. Preterm birth deprives the foetus of these high levels of allopregnanolone, which may contribute to the associated adverse effects on cerebellar development. Preterm birth alters expression of GABAA receptor subunit composition, which may further limit neurosteroid action. The objective of this study was to determine the effects of suppression of allopregnanolone levels on the markers of development and functional outcome. Pregnant guinea pigs were treated with finasteride at a dose (25¿mg/kg maternal weight) shown to suppress allopregnanolone between 60¿days of gestation until delivery (term ~71¿days). The cerebella from neonates, whose mothers were treated with finasteride or vehicle during pregnancy, were collected at postnatal age 8. Pups that received finasteride displayed significantly greater glial fibrillary acid protein area coverage and reduced GABAA receptor a6-subunit messenger RNA within the cerebellum than pups that were exposed to vehicle. These findings indicate that loss of neurosteroid action on the foetal brain in late gestation produces prolonged astrocyte activation and reductions in GABAA receptor a6-subunit expression. These changes may contribute to the long-term changes in function associated with preterm birth.
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Nova |
2017 |
Tolcos M, Petratos S, Hirst JJ, Wong F, Spencer SJ, Azhan A, et al., 'Blocked, delayed, or obstructed: What causes poor white matter development in intrauterine growth restricted infants?', Progress in Neurobiology, 154 62-77 (2017) [C1]
Poor white matter development in intrauterine growth restricted (IUGR) babies remains a major, untreated problem in neonatology. New therapies, guided by an understanding of the m... [more]
Poor white matter development in intrauterine growth restricted (IUGR) babies remains a major, untreated problem in neonatology. New therapies, guided by an understanding of the mechanisms that underlie normal and abnormal oligodendrocyte development and myelin formation, are required. Much of our knowledge of the mechanisms that underlie impaired myelination come from studies in adult demyelinating disease, preterm brain injury, or experimental models of hypoxia-ischemia. However, relatively less is known for IUGR which is surprising because IUGR is a leading cause of perinatal mortality and morbidity, second only to premature birth. IUGR is also a significant risk factor for the later development of cerebral palsy, and is a greater risk compared to some of the more traditionally researched antecedents ¿ asphyxia and inflammation. Recent evidence suggests that the white matter injury and reduced myelination in the brains of some preterm babies is due to impaired maturation of oligodendrocytes thereby resulting in the reduced capacity to synthesize myelin. Therefore, it is not surprising that the hypomyelination observable in the central nervous system of IUGR infants has similarly lead to investigations identifying a delay or blockade in the progress of maturation of oligodendrocytes in these infants. This review will discuss current ideas thought to account for the poor myelination often present in the neonate's brain following IUGR, and discuss novel interventions that are promising as treatments that promote oligodendrocyte maturation, and thereby repair the myelination deficits that otherwise persist into infancy and childhood and lead to neurodevelopmental abnormalities.
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Nova |
2017 |
Yawno T, Miller SL, Bennet L, Wong F, Hirst JJ, Fahey M, Walker DW, 'Ganaxolone : A New Treatment for Neonatal Seizures', FRONTIERS IN CELLULAR NEUROSCIENCE, 11 (2017) [C1]
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Nova |
2016 |
Bennett GA, Palliser HK, Walker D, Hirst J, 'Severity and timing: How prenatal stress exposure affects glial developmental, emotional behavioural and plasma neurosteroid responses in guinea pig offspring', Psychoneuroendocrinology, 70 47-57 (2016) [C1]
Prenatal stress has been associated with a variety of developmental changes in offspring, notably those associated with brain development and subsequent risk for neuropathologies ... [more]
Prenatal stress has been associated with a variety of developmental changes in offspring, notably those associated with brain development and subsequent risk for neuropathologies later in life. Recently, the importance of the timing and the severity of the stressor during pregnancy has been emphasized with neurosteroids including allopregnanolone implicated in the regulation of stress and also for endogenous neuroprotection in offspring.Prenatal stress was induced using strobe light exposure in pregnant guinea pigs (term 71 days) in three defined stress exposure groups (Gestational Age (GA)35-65, GA50-65 and GA60-65). Stress was induced for 2 h (9-11 am) every 5 days via strobe light exposure. A fetal cohort were euthanased at term with fetal brains and plasma collected. Anxiety-like behaviour was evaluated at 18 days of age in a separate cohort of offspring with brains and plasma collected at 21 days of age. Markers for mature oligodendrocytes and reactive astrocytes were measured in the CA1 region of the hippocampus and the subcortical white matter. The neurosteroid allopregnanolone was measured by radioimmunoassay in offspring plasma.In the CA1 region of the hippocampus, fetuses from all stress groups showed reduced expression of mature oligodendrocytes and reactive astrocytes. By juvenility, all male stress exposure groups had recovered to levels of unaffected controls with the exception of the GA35-65 stress group. In juvenile females, mature oligodendrocyte marker expression was reduced in all stress groups and reactive astrocyte expression was reduced in the GA35-65 and GA60-65 stress groups by juvenility. Increased reactive astrocyte expression was also apparent in the subcortical white matter in both sexes both at term and at juvenility. Prenatally stressed offspring spent less time exploring in the object exploration test and also entered the inner zone of the open field less than controls at 18 days of age. Circulating allopregnanolone concentrations were significantly reduced in GA35-65 and GA 60-65 stress exposed fetuses with those in the GA35-65 stress group remaining reduced by juvenility.This study has shown the effects of differing levels of prenatal stress severity and timing on glial development, emotional behaviour and plasma allopregnanolone concentrations in offspring.
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Nova |
2016 |
Hirst JJ, Cumberland AL, Shaw JC, Bennett GA, Kelleher MA, Walker DW, Palliser HK, 'Loss of neurosteroid-mediated protection following stress during fetal life', Journal of Steroid Biochemistry and Molecular Biology, 160 181-188 (2016) [C1]
Elevated levels of neurosteroids during late gestation protect the fetal brain from hypoxia/ischaemia and promote neurodevelopment. Suppression of allopregnanolone production duri... [more]
Elevated levels of neurosteroids during late gestation protect the fetal brain from hypoxia/ischaemia and promote neurodevelopment. Suppression of allopregnanolone production during pregnancy leads to the onset of seizure-like activity and potentiates hypoxia-induced brain injury. Markers of myelination are reduced and astrocyte activation is increased. The placenta has a key role in maintaining allopregnanolone concentrations in the fetal circulation and brain during gestation and levels decline markedly after both normal and preterm birth. This leads to the preterm neonate developing in a neurosteroid deficient environment between delivery and term equivalence. The expression of 5a-reductases is also lower in the fetus prior to term. These deficiencies in neurosteroid exposure may contribute to the increase in incidence of the adverse patterns of behaviour seen in children that are born preterm. Repeated exposure to glucocorticoid stimulation suppresses 5a-reductase expression and allopregnanolone levels in the fetus and results in reduced myelination. Both fetal growth restriction and prenatal maternal stress lead to increased cortisol concentrations in the maternal and fetal circulation. Prenatal stress results in reduced expression of key GABAA receptor subunits that normally heighten neurosteroid sensitivity. These stressors also result in altered placental allopregnanolone metabolism pathways. These findings suggest that reduced neurosteroid production and action in the perinatal period may contribute to some of the adverse neurodevelopmental and behavioural outcomes that result from these pregnancy compromises. Studies examining perinatal steroid supplementation therapy with non-metabolisable neurosteroid analogues to improve these outcomes are warranted.
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Nova |
2016 |
Shaw JC, Palliser HK, Dyson RM, Hirst JJ, Berry MJ, 'Long-term effects of preterm birth on behavior and neurosteroid sensitivity in the Guinea pig', Pediatric Research, 80 275-283 (2016) [C1]
Background: Ex-preterm children and adolescents are at risk of developing late-onset neurodevelopmental and behavioral disorders. The mechanisms by which this happens are poorly u... [more]
Background: Ex-preterm children and adolescents are at risk of developing late-onset neurodevelopmental and behavioral disorders. The mechanisms by which this happens are poorly understood and relevant animal models are required. Methods: Ex-preterm (delivered at 62 d gestation) and term (spontaneously delivered) juvenile Guinea pigs underwent behavioral testing at 25 d corrected postnatal age, with tissues collected at 28 d. Neurodevelopmental markers (myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP)) were analyzed in the hippocampus and subcortical white matter by immunohistochemistry. Gamma-aminobutyric acid A (GABA A) receptor subunit mRNA levels were quantified by reverse transcription polymerase chain reaction (RT-PCR), and salivary cortisol measured by enzyme-linked immunosorbent assay. Results: Preterm males travelled greater distances, were mobile for longer, spent more time investigating objects, and approached or interacted with familiar animals more than controls. Myelination and reactive astrocyte coverage was lower in the hippocampus and the subcortical white matter in preterm males. Hippocampal levels of the a5 subunit were also lower in the preterm male brain. Baseline salivary cortisol was higher for preterm males compared to controls. Conclusion: We conclude that juvenile ex-preterm male Guinea pigs exhibit a hyperactive phenotype and feature impaired neurodevelopment, making this a suitable model for future therapeutic studies.
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Nova |
2015 |
Bennett GA, Palliser HK, Shaw JC, Walker D, Hirst JJ, 'Prenatal stress alters hippocampal neuroglia and increases anxiety in childhood', Developmental Neuroscience, 37 533-545 (2015) [C1]
Prenatal stress has been associated with detrimental outcomes of pregnancy, including altered brain development leading to behavioural pathologies. The neurosteroid allopregnanolo... [more]
Prenatal stress has been associated with detrimental outcomes of pregnancy, including altered brain development leading to behavioural pathologies. The neurosteroid allopregnanolone has been implicated in mediating some of these adverse outcomes following prenatal stress due to its potent inhibitory and anxiolytic effects on the brain. The aims of the current study were to characterise key markers for brain development as well as behavioural parameters, adrenocortical responses to handling and possible neurosteroid influences towards outcomes in Guinea pig offspring in childhood. Pregnant Guinea pig dams were exposed to strobe light for 2 h (9-11 a.m.) on gestational days 50, 55, 60, and 65 and were left to deliver spontaneously at term and care for their litter. Behavioural testing (open-field test, object exploration test) of the offspring was performed at postnatal day 18 (with salivary cortisol and DHEA measured), and brains were collected at post-mortem on day 21. Markers of brain development myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) were assessed via immunohistochemistry, and the neurosteroid allopregnanolone and its rate-limiting enzymes 5a-reductase types 1 and 2 (5aR1/2) were measured in neonatal brains by radioimmunoassay, reverse transcriptase polymerase chain reaction (RT-PCR), and Western blot, respectively. Brain-derived neurotrophic factor protein was measured as a marker of synaptic plasticity, and GABAA receptor subunit expression was also assessed using RT-PCR. Neonates born from mothers stressed during late pregnancy showed a reduction in both MBP (p < 0.01) and GFAP (p < 0.05) expression in the CA1 region of the hippocampus at 21 days of age. Pups of prenatally stressed pregnancies also showed higher levels of anxiety and neophobic behaviours at the equivalent of childhood (p < 0.05). There were no significant changes observed in allopregnanolone levels, 5aR1/2 expression, or GABAA receptor subunit expression in prenatally stressed neonates compared to controls. This study shows alterations in markers of myelination and reactive astrocytes in the hippocampus of offspring exposed to prenatal stress. These changes are also observed in offspring that show increased anxiety behaviours at the equivalent of childhood, which indicates ongoing structural and functional postnatal changes after prenatal stress exposure.
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Nova |
2015 |
Shaw JC, Palliser HK, Walker DW, Hirst JJ, 'Preterm birth affects GABA
Modulation of gamma-aminobutyric acid A (GABAA) receptor signalling by the neurosteroid allopregnanolone has a major role in late gestation neurodevelopment. The objective of this... [more]
Modulation of gamma-aminobutyric acid A (GABAA) receptor signalling by the neurosteroid allopregnanolone has a major role in late gestation neurodevelopment. The objective of this study was to characterize the mRNA levels of GABAA receptor subunits (a4, a5, a6 and d) that are key to neurosteroid binding in the brain, following preterm birth. Myelination, measured by the myelin basic protein immunostaining, was used to assess maturity of the preterm brains. Foetal guinea pig brains were obtained at 62 days' gestational age (GA, preterm) or at term (69 days). Neonates were delivered by caesarean section, at 62 days GA and term, and maintained until tissue collection at 24 h of age. Subunit mRNA levels were quantified by RT-PCR in the hippocampus and cerebellum of foetal and neonatal brains. Levels of the a6 and d subunits were markedly lower in the cerebellum of preterm guinea pigs compared with term animals. Importantly, there was an increase in mRNA levels of these subunits during the foetal-to-neonatal transition at term, which was not seen following preterm birth. Myelination was lower in preterm neonatal brains, consistent with marked immaturity. Salivary cortisol concentrations, measured by EIA, were also higher for the preterm neonates, suggesting greater stress. We conclude that there is an adaptive increase in the levels of mRNA of the key GABAA receptor subunits involved in neurosteroid action after term birth, which may compensate for declining allopregnanolone levels. The lower levels of these subunits in preterm neonates may heighten the adverse effect of the premature decline in neurosteroid exposure.
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Nova |
2015 |
Palliser HK, Kelleher MA, Tolcos M, Walker DW, Hirst JJ, 'Effect of postnatal progesterone therapy following preterm birth on neurosteroid concentrations and cerebellar myelination in guinea pigs', Journal of Developmental Origins of Health and Disease, 6 350-361 (2015) [C1]
Allopregnanolone protects the fetal brain and promotes normal development including myelination. Preterm birth results in the early separation of the infant from the placenta and ... [more]
Allopregnanolone protects the fetal brain and promotes normal development including myelination. Preterm birth results in the early separation of the infant from the placenta and consequently a decline in blood and brain allopregnanolone concentrations. Progesterone therapy may increase allopregnanolone and lead to improved oligodendrocyte maturation. The objectives of this study were to examine the efficacy of progesterone replacement in augmenting allopregnanolone concentrations during the postnatal period and to assess the effect on cerebellar myelination - a region with significant postnatal development. Preterm guinea pig neonates delivered at 62 days of gestation by caesarean section received daily s.c. injections of vehicle (2-Hydroxypropyl-ß-cyclodextrin) or progesterone (16 mg/kg) for 8 days until term-equivalent age (TEA). Term delivered controls (PND1) received vehicle. Neonatal condition/wellbeing was scored, and salivary progesterone was sampled over the postnatal period. Brain and plasma allopregnanolone concentrations were measured by radioimmunoassay; cortisol and progesterone concentrations were determined by enzyme immunoassay; and myelin basic protein (MBP), proteolipid protein (PLP), oligodendroctye transcription factor 2 (OLIG2) and platelet-derived growth factor receptor-a (PDGFRa) were quantified by immunohistochemistry and western blot. Brain allopregnanolone concentrations were increased in progesterone-treated neonates. Plasma progesterone and cortisol concentrations were elevated in progesterone-treated male neonates. Progesterone treatment decreased MBP and PLP in lobule X of the cerebellum and total cerebellar OLIG2 and PDGFRa in males but not females at TEA compared with term animals. We conclude that progesterone treatment increases brain allopregnanolone concentrations, but also increases cortisol levels in males, which may disrupt developmental processes. Consideration should be given to the use of non-metabolizable neurosteroid agonists.
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Nova |
2014 |
Brunton PJ, Russell JA, Hirst JJ, 'Allopregnanolone in the brain: Protecting pregnancy and birth outcomes', PROGRESS IN NEUROBIOLOGY, 113 106-136 (2014) [C1]
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Nova |
2014 |
Hirst JJ, Kelleher MA, Walker DW, Palliser HK, 'Neuroactive steroids in pregnancy: Key regulatory and protective roles in the foetal brain', Journal of Steroid Biochemistry and Molecular Biology, 139 144-153 (2014) [C1]
Neuroactive steroid concentrations are remarkably high in the foetal brain during late gestation. These concentrations are maintained by placental progesterone synthesis and the i... [more]
Neuroactive steroid concentrations are remarkably high in the foetal brain during late gestation. These concentrations are maintained by placental progesterone synthesis and the interaction of enzymes in the placenta and foetal brain. 5a-Pregnane-3a-ol-20-one (allopregnanolone) is a key neuroactive steroid during foetal life, although other 3a-hydroxy- pregnanes may make an additional contribution to neuroactive steroid action. Allopregnanolone modulates GABAergic inhibition to maintain a suppressive action on the foetal brain during late gestation. This action suppresses foetal behaviour and maintains the appropriate balance of foetal sleep-like behaviours, which in turn are important to normal neurodevelopment. Neuroactive steroid-induced suppression of excitability has a key role in protecting the foetal brain from acute hypoxia/ischaemia insults. Hypoxia-induced brain injury is markedly increased if neuroactive steroid levels are suppressed and there is increased seizure activity. There is also a rapid increase in allopregnanolone synthesis and hence levels in response to acute stress that acts as an endogenous protective mechanism. Allopregnanolone has a trophic role in regulating development, maintaining normal levels of apoptosis and increasing myelination during late gestation in the brain. In contrast, chronic foetal stressors, including intrauterine growth restriction, do not increase neuroactive steroid levels in the brain and exposure to repeated synthetic corticosteroids reduce neuroactive steroid levels. The reduced availability of neuroactive steroids may contribute to the adverse effects of chronic stressors on the foetal and newborn brain. Preterm birth also deprives the foetus of neuroactive steroid mediated protection and may increase vulnerability to brain injury and suboptimal development. These finding suggest replacement therapies should be explored. This article is part of a Special Issue entitled 'Pregnancy and steroids © 2013 Elsevier Ltd. All rights reserved.
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Nova |
2014 |
Hutton LC, Yan E, Yawno T, Castillo-Melendez M, Hirst JJ, Walker DW, 'Injury of the Developing Cerebellum: A Brief Review of the Effects of Endotoxin and Asphyxial Challenges in the Late Gestation Sheep Fetus', Cerebellum, 13 777-786 (2014) [C1]
The vulnerability of the fetal and newborn brain to events in utero or at birth that cause damage arising from perturbations of cerebral blood flow and metabolism, such as the acc... [more]
The vulnerability of the fetal and newborn brain to events in utero or at birth that cause damage arising from perturbations of cerebral blood flow and metabolism, such as the accumulation of free radicals and excitatory transmitters to neurotoxic levels, has received considerable attention over the last few decades. Attention has usually been on the damage to cerebral structures, particularly, periventricular white matter. The rapid growth of the cerebellum in the latter half of fetal life in species with long gestations, such as the human and sheep, suggests that this may be a particularly important time for the development of cerebellar structure and function. In this short review, we summarize data from recent studies with fetal sheep showing that the developing cerebellum is particularly sensitive to infectious processes, chronic hypoxia and asphyxia. The data demonstrates that the cerebellum should be further studied in insults of this nature as it responds differently to the remainder of the brain. Damage to this region of the brain has implications not only for the development of motor control and posture, but also for higher cognitive processes and the subsequent development of complex behaviours, such as learning, memory and attention.
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Nova |
2014 |
Welsh TN, Hirst JJ, Palliser H, Zakar T, 'Progesterone Receptor Expression Declines in the Guinea Pig Uterus during Functional Progesterone Withdrawal and in Response to Prostaglandins', PLOS ONE, 9 (2014) [C1]
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Nova |
2014 |
Palliser HK, Kelleher MA, Welsh TN, Zakar T, Hirst JJ, 'Mechanisms Leading to Increased Risk of Preterm Birth in Growth-Restricted Guinea Pig Pregnancies', REPRODUCTIVE SCIENCES, 21 269-276 (2014) [C1]
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Nova |
2014 |
Cumberland AL, Palliser HK, Hirst JJ, 'Increased placental neurosteroidogenic gene expression precedes poor outcome in the preterm guinea pig', Journal of Developmental Origins of Health and Disease, 5 74-78 (2014) [C1]
Placental 5a-reductase (5aR) is influenced by in utero compromises and has a role in regulating neuroactive steroid concentrations in the fetus. The objective of this study was to... [more]
Placental 5a-reductase (5aR) is influenced by in utero compromises and has a role in regulating neuroactive steroid concentrations in the fetus. The objective of this study was to determine if changes in placental 5aR were associated with neonatal outcome after birth. Guinea pigs were delivered by cesarean section at term (GA69, n=22) or preterm (GA62, n=36) and the placenta collected. Preterm neonates were maintained for 24 h unless their condition deteriorated before this time. Enzyme mRNA expression of 5aR type-1 and 5aR type-2 were determined using real-time PCR. All preterm neonates had significantly higher 5aR2 expression in their placenta compared with placentae from term neonates (P<0.0001). Expression was also markedly higher in the placentae from neonates that did not survive until 24 h, compared with surviving preterm neonates (P=0.04). These findings suggest differences of in utero neurosteroidogenic capacity between surviving and non-surviving preterm guinea pig neonates. The increased 5aR2 mRNA expression in the placenta of non-survivors suggests an induction of the neurosteroid pathway due to prior exposure to an in utero compromise, with such exposure possibly a predisposing factor that contributed to their poor ex utero outcome. © 2014 Cambridge University Press.
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Nova |
2013 |
Bennett GA, Palliser HK, Saxby B, Walker DW, Hirst JJ, 'Effects of Prenatal Stress on Fetal Neurodevelopment and Responses to Maternal Neurosteroid Treatment in Guinea Pigs', DEVELOPMENTAL NEUROSCIENCE, 35 416-426 (2013) [C1]
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Nova |
2013 |
Mitchell CM, Sykes SD, Pan X, Pringle KG, Lumbers ER, Hirst JJ, Zakar T, 'Inflammatory and steroid receptor gene methylation in the human amnion and decidua', JOURNAL OF MOLECULAR ENDOCRINOLOGY, 50 267-277 (2013) [C1]
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Nova |
2013 |
Kelleher MA, Hirst JJ, Palliser HK, 'Changes in neuroactive steroid concentrations after preterm delivery in the guinea pig', Reproductive Sciences, 20 1365-1375 (2013) [C1]
Background: Preterm birth is a major cause of neurodevelopmental disorders. Allopregnanolone, a key metabolite of progesterone, has neuroprotective and developmental effects in th... [more]
Background: Preterm birth is a major cause of neurodevelopmental disorders. Allopregnanolone, a key metabolite of progesterone, has neuroprotective and developmental effects in the brain. The objectives of this study were to measure the neuroactive steroid concentrations following preterm delivery in a neonatal guinea pig model and assess the potential for postnatal progesterone replacement therapy to affect neuroactive steroid brain and plasma concentrations in preterm neonates. Methods: Preterm (62-63 days) and term (69 days) guinea pig pups were delivered by cesarean section and tissue was collected at 24 hours. Plasma progesterone, cortisol, allopregnanolone, and brain allopregnanolone concentrations were measured by immunoassay. Brain 5a-reductase (5aR) expression was determined by Western blot. Neurodevelopmental maturity of preterm neonates was assessed by immunohistochemistry staining for myelination, glial cells, and neurons. Results: Brain allopregnanolone concentrations were significantly reduced after birth in both preterm and term neonates. Postnatal progesterone treatment in preterm neonates increased brain and plasma allopregnanolone concentrations. Preterm neonates had reduced myelination, low birth weight, and high mortality compared to term neonates. Brain 5aR expression was also significantly reduced in neonates compared to fetal expression. Conclusions: Delivery results in a loss of neuroactive steroid concentrations resulting in a premature reduction in brain allopregnanolone in preterm neonates. Postnatal progesterone therapy reestablished neuroactive steroid levels in preterm brains, a finding that has implications for postnatal growth following preterm birth that occurs at a time of neurodevelopmental immaturity. © 2013 The Author(s).
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Nova |
2012 |
Fleiss B, Parkington HC, Coleman HA, Dickinson H, Yawno T, Castillo-Melendez M, et al., 'Effect of maternal administration of allopregnanolone before birth asphyxia on neonatal hippocampal function in the spiny mouse', Brain Research, 1433 9-19 (2012) [C1]
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Nova |
2012 |
Palliser HK, Yates DM, Hirst JJ, 'Progesterone receptor isoform expression in response to in utero growth restriction in the fetal guinea pig brain', Neuroendocrinology, 96 60-67 (2012) [C1]
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Nova |
2012 |
Dyson RM, Palliser HK, Kelleher MA, Hirst JJ, Wright IM, 'The guinea pig as an animal model for studying perinatal changes in microvascular function', Pediatric Research, 71 20-24 (2012) [C1]
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Nova |
2012 |
Welsh T, Caritis S, Hirst J, Mesiano S, Zakar T, 'Progesterone Withdrawal in the Pregnant Guinea Pig Is Mediated by Decreased Uterine PR Expression and Stimulated by Prostaglandins In Vivo', REPRODUCTIVE SCIENCES, 19 192A-192A (2012) [E3] |
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2012 |
Welsh T, Paul J, Palliser H, Hirst J, Mesiano S, Zakar T, 'PGDH Expression Decreases at Term before Labor Onset in Guinea Pig Fetal Membranes', REPRODUCTIVE SCIENCES, 19 192A-192A (2012) [C3]
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2012 |
Mitchell CM, Chai S, Madsen G, Hirst JJ, Zakar T, 'Bivalent Epigenetic Modifications Regulate PTGS2 Expression during Gestation in the Amnion', REPRODUCTIVE SCIENCES, 19 299A-299A (2012) [E3] |
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2012 |
Welsh TN, Paul JW, Palliser HK, Tabatabaeehatambakhsh SH, Hirst JJ, Mesiano S, Zakar T, '15-hydroxyprostaglandin dehydrogenase expression and localization in guinea pig gestational tissues during late pregnancy and parturition', Reproductive Sciences, 19 1099-1109 (2012) [C1]
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Nova |
2011 |
Pringle KG, Zakar T, Roach DM, Mitchell CM, Hirst JJ, Lumbers ER, 'Molecular evidence of a (pro)renin/(pro)renin receptor system in human intrauterine tissues in pregnancy and its association with PGHS-2', Journal of the Renin-Angiotensin-Aldosterone System, 12 304-310 (2011) [C1]
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Nova |
2011 |
Marques FZ, Pringle KG, Conquest AL, Hirst JJ, Markus MA, Sarris M, et al., 'Molecular characterization of renin-angiotensin system components in human intrauterine tissues and fetal membranes from vaginal delivery and cesarean section', Placenta, 32 214-221 (2011) [C1]
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Nova |
2011 |
Mitchell CM, Johnson R, Bisits AM, Hirst JJ, Zakar T, 'PTGS2 (Prostaglandin Endoperoxide Synthase-2) expression in term human amnion in vivo involves rapid mRNA turnover, polymerase-II 5 '-pausing, and glucocorticoid transrepression', Endocrinology, 152 2113-2122 (2011) [C1]
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Nova |
2011 |
Kelleher MA, Palliser HK, Walker DW, Hirst JJ, 'Sex-dependent effect of a low neurosteroid environment and intrauterine growth restriction on foetal guinea pig brain development', Journal of Endocrinology, 208 301-309 (2011) [C1]
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Nova |
2011 |
Yawno T, Yan EB, Hirst JJ, Walker DW, 'Neuroactive steroids induce changes in fetal sheep behavior during normoxic and asphyxic states', Stress, 14 13-22 (2011) [C1]
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Nova |
2011 |
Frye CA, Hirst JJ, Brunton PJ, Russell JA, 'Neurosteroids for a successful pregnancy', Stress, 14 1-5 (2011) [C3]
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Nova |
2010 |
Palliser HK, Zakar T, Symonds IM, Hirst JJ, 'Progesterone receptor isoform expression in the guinea pig myometrium from normal and growth restricted pregnancies', Reproductive Sciences, 17 776-782 (2010) [C1]
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Nova |
2010 |
Dellios NL, Lappas M, Young IR, Palliser HK, Hirst JJ, Oliva K, et al., 'Increased expression of alpha-enolase in cervico-vaginal fluid during labour', European Journal of Obstetrics Gynecology and Reproductive Biology, 153 16-22 (2010) [C1]
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Nova |
2010 |
McKendry AA, Palliser HK, Yates DM, Walker DW, Hirst JJ, 'The effect of betamethasone treatment on neuroactive steroid synthesis in a foetal guinea pig model of growth restriction', Journal of Neuroendocrinology, 22 166-174 (2010) [C1]
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Nova |
2009 |
Yawno T, Hirst JJ, Castillo-Melendez M, Walker DW, 'Role of neurosteroids in regulating cell death and proliferation in the late gestation fetal brain', Neuroscience, 163 838-847 (2009) [C1]
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Nova |
2009 |
Hirst JJ, Walker DW, Yawno T, Palliser HK, 'Stress in pregnancy: A role for neuroactive steroids in protecting the fetal and neonatal brain', Developmental Neuroscience, 31 363-377 (2009) [C1]
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Nova |
2009 |
Vu TT, Hirst JJ, Stark MJ, Wright IM, Palliser HK, Hodyl NA, Clifton VL, 'Changes in human placental 5 alpha-reductase isoenzyme expression with advancing gestation: Effects of fetal sex and glucocorticoid exposure', Reproduction Fertility and Development, 21 599-607 (2009) [C1]
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Nova |
2009 |
Winnall WR, Muir JA, Liew S, Hirst JJ, Meachem SJ, Hedger MP, 'Effects of chronic celecoxib on testicular function in normal and lipopolysaccharide-treated rats', International Journal of Andrology, 32 542-555 (2009) [C1]
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Nova |
2008 |
Westcott KT, Hirst JJ, Ciurej I, Walker DW, Wlodek ME, 'Brain allopregnanolone in the fetal and postnatal rat in response to uteroplacental insufficiency', Neuroendocrinology, 88 287-292 (2008) [C1]
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Nova |
2008 |
Hirst JJ, Palliser HK, Roach DM, Yawno T, Walker DW, 'Neurosteroids in the fetus and neonate: Potential protective role in compromised pregnancies', Neurochemistry International, 52 602-610 (2008) [C1]
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Nova |
2007 |
Yawno T, Yan EB, Walker DW, Hirst JJ, 'Inhibition of neurosteroid synthesis increases asphyxia-induced brain injury in the late gestation fetal sheep', Neuroscience, 146 1726-1733 (2007) [C1]
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2007 |
Hutton LC, Yan E, Yawno T, Castillo-Melendez M, Hirst JJ, Walker DW, 'Injury of the developing cerebellum: A brief review of the effects of endotoxin and asphyxial challenges in the late gestation sheep fetus.', Cerebellum (London, England), 1-10 (2007)
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2007 |
Young R, Rice GE, Palliser HK, Ayhan M, Dellios NL, Hirst JJ, 'Identification of bactenecin-1 in cervicovaginal fluid by two-dimensional electrophoresis in an ovine model of preterm labour', Proteomics, 7 281-288 (2007) [C1]
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2007 |
Smith R, Van Helden DF, Hirst JJ, Zakar T, Read MA, Chan EC, et al., 'Pathological interactions with the timing of birth and uterine activation', Australian & New Zealand Journal of Obstetrics & Gynaecology, 47 430-437 (2007) [C1]
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2007 |
Winnall WR, Ali U, O'Bryan MK, Hirst JJ, Whiley PAF, Muir JA, Hedger MP, 'Constitutive expression of prostaglandin-endoperoxide synthase 2 by somatic and spermatogenic cells is responsible for prostaglandin E2 production in the adult rat testis', Biology of Reproduction, 76 759-768 (2007) [C1]
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2006 |
Hirst JJ, Yawno T, Nguyen P, Walker DW, 'Stress in Pregnancy Activates Neurosteroid Production in the Fetal Brain', Neuroendocrinology, 84 264-274 (2006) [C1]
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2006 |
Ochsenkuhn R, O'Connor AE, Hirst JJ, Baker HWG, De Kretser DM, Hedger MP, 'The relationship between immunosuppressive activity and immunoregulatory cytokines in seminal plasma: Influence of sperm autoimmunity and seminal leukocytes', Journal of reproductive immunology, 71 57-74 (2006) [C1]
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2006 |
Palliser HK, Dellios N, Escalona R, Ooi G, Rice GE, Hirst J, Young IR, 'Labor-Associated Regulation of Prostaglandin E and F Synthesis and Action in the Ovine Amnion and Cervix', Reproductive Sciences, 13 19-24 (2006) [C1]
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2006 |
Billiards SS, Guyen PN, Scheerlinck J-P, Phillips DJ, Canny BJ, Walker DW, Hirst JJ, 'Hypoxia potentiates endotoxin-induced allopregnanolone concentrations in the newborn brain', Biology of the Neonate, 90 258-267 (2006) [C1]
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2005 |
Manuepillai U, Ligam P, Smythe GA, Wallace EM, Phillips D, Guilemin GJ, et al., 'Identification of kynurenine pathway enzyme mRNAs and metabolites in human placenta: Up-regulation by inflammatory stimuli and with clinical infection', American Journal of Obstetrics and Gynecology, 192 280-288 (2005) [C1]
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2005 |
Hirst JJ, Parkington HC, Young IR, Palliser HK, Peri KG, Olsen DM, 'Delay of preterm birth in sheep by THG113.31, a prostaglandin F2[a] receptor antagonist', American Journal of Obstetrics and Gynecology, 193 256-266 (2005) [C1]
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2005 |
Palliser HK, Hirst J, Ooi GT, Rice GE, Escalona RM, Dellios NL, et al., 'Prostaglandin E and F receptor expression and myometrial sensitivity at labour onset in sheep', Biology of Reproduction, 72 937-943 (2005) [C1]
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2004 |
Nguyen PN, Young IR, Walker DW, Hirst J, 'Allopregnanolone in the brain and blood after disruption of the hypothalamic-pituitary-adrenal axis in fetal sheep', Journal of Endocrinology, 182 81-88 (2004) [C1]
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2004 |
Palliser HK, Dellios N, Escalona R, Ooi G, Rice GE, Hirst J, Young IR, 'Changes in the Expression of prostaglandin E and F synthases at induced and spontaneous labour onset in the sheep', Journal of Endocrinology, 180 469-477 (2004) [C1]
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2004 |
Nguyen PN, Yan EB, Castillo-Melendez M, Walker DW, Hirst J, 'Increased allopregnanolone levels in the fetal sheep brain following umbilical cord occlusion', The Journal of Physiology, 560 593-602 (2004) [C1]
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2004 |
Yan EB, Nichols T, Hirst J, Walker DW, 'Cerebrovascular Responses in the Fetal Sheep Brain to Low-Dose Endotoxin', Pediatric Research, 55 855-863 (2004) [C1]
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2003 |
Hirst J, Scheerlinbeck JP, Phillips DJ, Jenkin G, Grigsby PL, 'Fetal responses to maternal and intra-amniotic administration of lipopolysaccharide administration in sheep', Biology of Reproduction, 68 1695-1702 (2003) [C1]
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2003 |
Crossley KJ, Nitsos I, Walker DW, Lawrence AJ, Beart PM, Hirst J, 'Steroid-sensitive GABAA receptors in the fetal sheep brain', Neuropharmacology, 45 461-472 (2003) [C1]
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2003 |
Nguyen PN, Billiards SS, Walker DW, Hirst J, 'Changes in 5[alpha]-pregnane steroids and neurosteroidogenic enzyme expression in the perinatal sheep', Pediatric Research, 53 956-964 (2003) [C1]
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2003 |
Nguyen PN, Billiards SS, Walker DW, Hirst J, 'Changes in 5[alpha]-pregnane steroids and neurosteroidogenic enzyme expression in fetal sheep with umbilicoplacental embolisation', Pediatric Research, 54 840-847 (2003) [C1]
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2003 |
Olson DM, Zaragoza DB, Shallow MC, Cook JL, Mitchell BF, Grigsby PL, Hirst J, 'Myometrial activation and preterm labour: evidence supporting a role for the prostaglandin F receptor--a review', Placenta, 24 47-54 (2003) [C1]
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2002 |
Billiards SS, Walker DW, Canny BJ, Hirst J, 'Endotoxin Increases Sleep and Brain Allopregnanolone Concentrations in Newborn Lambs', Paediatric Research, 52 892-899 (2002) [C1]
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2002 |
Lee B, Hirst JJ, Walker DW, 'Prostaglandin D synthase in the prenatal ovine brain and effects of its inhibition with selenium chloride on fetal sleep/wake activity in utero', JOURNAL OF NEUROSCIENCE, 22 5679-5686 (2002)
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2002 |
Lee B, Hirst J, Walker DW, 'Inhibition of prostaglandin D synthase by intraventriculalar administration of selenium chloride induces behavioural arousal in the ovine fetus. 5679-5686 (2002) [C1] |
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2002 |
Haluska GJ, Wells T, Hirst J, Brenner R, Sadowsky M, Novy DW, 'Progesterone receptor localization and isoforms in myometrium, decidua and fetal membranes from rhesus monkeys: evidence for functional progesterone withdrawal at parturition.', Journal of Society for Gynaecological Investigation, 9 125-136 (2002) [C1]
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2002 |
Haluska GJ, Wells TR, Hirst JJ, Brenner RM, Sadowsky DW, Novy MJ, 'Progesterone receptor Localization and Isoforms in Myometrium, Decidua, and Fetal Membranes From Rhesus Macaques: Evidence for Function Progresterone Withdrawal at Parturtion', Journal of the Society for Gynecologic Investigation, 9 125-136 (2002)
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2001 |
Nicol MB, Hirst JJ, Walker DW, 'Effect of finasteride on behavioural arousal and somatosensory evoked potentials in fetal sheep', NEUROSCIENCE LETTERS, 306 13-16 (2001)
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2001 |
Scott JE, Grigsby PL, Hirst JJ, Jenkin G, 'Inhibition of Prostaglandin Synthesis and Its Effect on Uterine Activity During Established Premature Labor in Sheep', Journal of the Society for Gynecologic Investigation, 8 266-276 (2001)
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2001 |
Scott JE, Grigsby PL, Hirst JJ, Jenkin G, 'Inhibition of prostaglandin synthesis and its effect on uterine activity during established premature labor in sheep', JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION, 8 266-276 (2001)
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2001 |
Scott J, Grigsby P, Hirst J, Jenkin G, 'Inhibition of prostaglandin release and its effect on uterine activity during induced premature labour in late pregnant sheep. 266-276 (2001) [C1] |
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2001 |
Nicol MB, Walker DW, Hirst J, 'Effect of the 5a-reductase, finasteride, on fetal behavioural state.', Neuroscience Letters, 306 13-16 (2001) [C1] |
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2000 |
Crossley KJ, Walker DW, Beart PM, Hirst JJ, 'Characterisation of GABA(A) receptors in fetal, neonatal and adult ovine brain: region and age related changes and the effects of allopregnanolone', NEUROPHARMACOLOGY, 39 1514-1522 (2000)
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2000 |
Hirst JJ, Egodagamage KC, Walker DW, 'Effect of a neuroactive steroid infused into the cerebral ventricles of fetal sheep in utero using small infusion volumes', JOURNAL OF NEUROSCIENCE METHODS, 97 37-44 (2000)
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2000 |
Walker DW, Lee B, Hirst J, 'Inhibition of prostaglandin D synthase in fetal sheep brain with selenium chloride induces arousal.', FASEB JOURNAL, 14 A388-A388 (2000) |
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2000 |
Hirst JJ, Petratos S, Mendis S, Walker DW, 'Neuroactive steroid synthesis in the ovine fetal and newborn brain', FASEB JOURNAL, 14 A654-A654 (2000) |
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2000 |
Petratos S, Hirst JJ, Mendis S, Anikijenko P, Walker DW, 'Localization of P450scc and 5 alpha-reductase type-2 in the cerebellum of fetal and newborn sheep', DEVELOPMENTAL BRAIN RESEARCH, 123 81-86 (2000)
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2000 |
Ross-McGill H, Hewison J, Hirst J, Dowswell T, Holt A, Brunskill P, Thornton JG, 'Antenatal home blood pressure monitoring: a pilot randomised controlled trial', BRITISH JOURNAL OF OBSTETRICS AND GYNAECOLOGY, 107 217-221 (2000)
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2000 |
Grigsby PL, Poore KR, Hirst JJ, Jenkin G, 'Inhibition of premature labor in sheep by a combined treatment of nimesulide, a prostaglandin synthase type 2 inhibitor, and atosiban, an oxytocin receptor antagonist', AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY, 183 649-657 (2000)
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1999 |
Poore KR, Young IR, Hirst JJ, 'Efficacy of the selective prostaglandin synthase type 2 inhibitor nimesulide in blocking basal prostaglandin production and delaying glucocorticoid-induced premature labor in sheep', AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY, 180 1244-1253 (1999)
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1999 |
Nicol MB, Hirst JJ, Walker D, 'Effects of pregnanolone on behavioural parameters and the responses to GABA(A) receptor antagonists in the late gestation fetal sheep', NEUROPHARMACOLOGY, 38 49-63 (1999)
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1998 |
Nicol MB, Hirst JJ, Walker DW, 'Effect of pregnane steroids on electrocortical activity and somatosensory evoked potentials in fetal sheep', NEUROSCIENCE LETTERS, 253 111-114 (1998)
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1998 |
Hirst JJ, Mijovic JE, Zakar T, Olson DM, 'Prostaglandin endoperoxide H synthase-1 and -2 mRNA levels and enzyme activity in human decidua at term labor', JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION, 5 13-20 (1998)
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1997 |
Nicol MB, Hirst JJ, Walker D, Thorburn GD, 'Effect of alteration of maternal plasma progesterone concentrations on fetal behavioural state during late gestation', JOURNAL OF ENDOCRINOLOGY, 152 379-386 (1997)
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1997 |
Dowswell T, Piercy J, Hirst J, Hewison J, Lilford R, 'Short postnatal hospital stay: Implications for women and service providers', JOURNAL OF PUBLIC HEALTH MEDICINE, 19 132-136 (1997)
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1997 |
Crossley KJ, Nicol MB, Hirst JJ, Walker DW, Thorburn GD, 'Suppression of arousal by progesterone in fetal sheep', REPRODUCTION FERTILITY AND DEVELOPMENT, 9 767-773 (1997)
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1996 |
Hirst JJ, Thorburn GD, 'Initiation of Parturition in Non-Human Primates 61-87 (1996)
The endocrine regulation of pregnancy and the timing of labor onset differs markedly between species. Non-human primates are the closest experimental animals to humans and, theref... [more]
The endocrine regulation of pregnancy and the timing of labor onset differs markedly between species. Non-human primates are the closest experimental animals to humans and, therefore, studies of these species are of great value in bridging gaps in knowledge created by this divergence. The principal advantage of non-human primates for the study of pregnancy is the ability to perform maternal and fetal repetitive sampling protocols. Studies with chronically catheterized fetal rhesus monkeys have shown that labor begins at normal term following the death of the fetus, although the spread of delivery times around normal term is increased. These observations indicate that the fetus does not influence mean gestational length, but has a permissive role in the fine-tuning of the timing of labor onset. There is no decline in maternal progesterone concentration prior to labor onset in primates, a finding which is in marked contrast to other species. Since there is no fall in the sensitivity of the intrauterine tissues to progesterone, primate intrauterine tissues may be sufficiently refractory to progesterone to allow the initiation of labor in the presence of high gestational progesterone concentrations. There is a marginal increase in the concentration of estrogens as term approaches such that the ratio of estrogens to progesterone rises slightly. This rise may be responsible for the increase in gap junctions and oxytocin receptors that is observed prior to labor onset. Non-human primate studies have provided convincing evidence supporting a role for prostaglandins as the primary stimulatory factor in the initiation of labor. Longitudinal studies in the rhesus monkey have demonstrated that there is a steady rise in prostaglandin concentrations in the amniotic fluid before the onset of labor. These observations suggest that rising prostaglandin concentrations in the intrauterine tissues and amniotic fluid ultimately lead to the initiation of labor. Increasing intrauterine prostaglandin synthesis may be exclusively responsible for initiation of labor following the death of the fetus. Increased maternal oxytocin secretion most likely has a role in the stimulation of decidual prostaglandin synthesis at the time of spontaneous labor onset, whereas an increase in cytokine levels within the uterine compartment may be responsible for the stimulation of prostaglandin production following intrauterine infection. Pregnant rhesus monkeys exhibit episodes of markedly increased uterine activity at night which are driven by elevated oxytocin concentrations in the maternal plasma. The magnitude of the nocturnal rise in oxytocin concentrations increases as term approaches and leads to greater levels of nocturnal uterine activity. The development of nocturnal uterine activity episodes requires the presence of a suitably stimulated level of myometrial oxytocin receptors. This stimulation, in turn, is generated by the increasingly estrogenic environment produced by the fetus near term and may represent the contribution of the fetus to the timing of labor onset. The heightened level of nocturnal oxytocin secretion in the presence of elevated oxytocin receptor concentrations leads to a further increase in nocturnal uterine activity episodes near term. Once adequate levels of prostaglandins are attained within the intrauterine tissues, oxytocin-driven nocturnal uterine activity progresses to labor and delivery in non-human primate species. © 1996 Jai Press Inc.
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1996 |
Zakar T, Olson DM, Teixeira FJ, Hirst JJ, 'Regulation of prostaglandin endoperoxide H
Increased production of prostaglandins by the gestational tissues is pivotal for the initiation and maintenance of human labour. A major source of prostaglandins in the pregnant h... [more]
Increased production of prostaglandins by the gestational tissues is pivotal for the initiation and maintenance of human labour. A major source of prostaglandins in the pregnant human uterus is the amnion membrane, which synthesizes increased amounts of prostaglandin E2 (PGE2) at parturition. We have found that the activity of prostaglandin endoperoxide H2 synthase (PGHS), the enzyme catalyzing the committing step of prostanoid biosynthesis, increases significantly in the amnion at term and preterm labour, and also prior to the onset of clinical labour at term. Furthermore, the abundance of the mRNA encoding the inducible PGHS-2 isoenzyme was higher in the amnion after spontaneous delivery that before labour. The level of the constitutive PGHS-1 mRNA remained unchanged. In addition, we found a significant positive correlation between PGHS activity and the level of PGHS-2 mRNA, but not of PGHS-1 mRNA, in the individual tissue samples, also indicating that PGHS-2 was selectively induced in the amnion membrane at labour. The regulation of PGHS expression by agonists was studied using primary cultures of amnion cells. Glucocorticoid treatment enhanced the activity of PGHS and the level of PGHS-2 mRNA in the cultured cells, without affecting PGHS-1 mRNA abundance. The stimulation was glucocorticoid specific and was blocked by the glucocorticoid receptor antagonist RU486, suggesting that it was mediated by the glucocorticoid receptor. Inhibition of protein synthesis did not block the accumulation of PGHS-2 mRNA showing that the steroid acted directly, without inducing an intervening protein. Protein kinase C activator and protein phosphatase inhibitor compounds and epidermal growth factor also promoted PGHS-2.
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1995 |
Zakar T, Hirst JJ, Mijovic JE, Olson DM, 'Glucocorticoids stimulate the expression of prostaglandin endoperoxide H synthase-2 in amnion cells.', Endocrinology, 136 1610-1619 (1995)
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1995 |
Hirst JJ, Teixeira FJ, Zakar T, Olson DM, 'Prostaglandin endoperoxide-H synthase-1 and -2 messenger ribonucleic acid levels in human amnion with spontaneous labor onset.', The Journal of Clinical Endocrinology & Metabolism, 80 517-523 (1995)
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1995 |
ZAKAR T, HIRST JJ, MIJOVIC JE, OLSON DM, 'GLUCOCORTICOIDS STIMULATE THE EXPRESSION OF PROSTAGLANDIN ENDOPEROXIDE-H SYNTHASE-2 IN AMNION CELLS', ENDOCRINOLOGY, 136 1610-1619 (1995)
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1995 |
HIRST JJ, TEIXEIRA FJ, ZAKAR T, OLSON DM, 'PROSTAGLANDIN ENDOPEROXIDE-H SYNTHASE-1 AND SYNTHASE-2 MESSENGER-RIBONUCLEIC-ACID LEVELS IN HUMAN AMNION WITH SPONTANEOUS LABOR ONSET', JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 80 517-523 (1995)
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1994 |
Teixeira FJ, Zakar T, Hirst JJ, Guo F, Sadowsky DW, Machin G, et al., 'Prostaglandin endoperoxide-H synthase (PGHS) activity and immunoreactive PGHS-1 and PGHS-2 levels in human amnion throughout gestation, at term, and during labor.', The Journal of Clinical Endocrinology & Metabolism, 78 1396-1402 (1994)
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1994 |
TEIXEIRA FJ, ZAKAR T, HIRST JJ, GUO F, SADOWSKY DW, MACHIN G, et al., 'PROSTAGLANDIN ENDOPEROXIDE-H SYNTHASE (PGHS) ACTIVITY AND IMMUNOREACTIVE PGHS-1 AND PGHS-2 LEVELS IN HUMAN AMNION THROUGHOUT GESTATION, AT TERM, AND DURING LABOR', JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 78 1396-1402 (1994)
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1994 |
ZAKAR T, TEIXEIRA FJ, HIRST JJ, GUO F, MACLEOD EA, OLSON DM, 'REGULATION OF PROSTAGLANDIN ENDOPEROXIDE-H SYNTHASE BY GLUCOCORTICOIDS AND ACTIVATORS OF PROTEIN-KINASE-C IN THE HUMAN AMNION', JOURNAL OF REPRODUCTION AND FERTILITY, 100 43-50 (1994)
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1993 |
Hirst JJ, Chibbar R, Mitchell BF, 'Role of oxytocin in the regulation of uterine activity during pregnancy and in the initiation of labor', Seminars in Reproductive Endocrinology, 11 219-233 (1993)
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1993 |
Slayden OD, Hirst JJ, Brenner RM, 'Estrogen action in the reproductive tract of rhesus monkeys during antiprogestin treatment.', Endocrinology, 132 1845-1856 (1993)
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1993 |
HIRST JJ, HALUSKA GJ, COOK MJ, NOVY MJ, 'PLASMA OXYTOCIN AND NOCTURNAL UTERINE ACTIVITY - MATERNAL BUT NOT FETAL CONCENTRATIONS INCREASE PROGRESSIVELY DURING LATE PREGNANCY AND DELIVERY IN RHESUS-MONKEYS', AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY, 169 415-422 (1993)
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1993 |
SLAYDEN OD, HIRST JJ, BRENNER RM, 'ESTROGEN ACTION IN THE REPRODUCTIVE-TRACT OF RHESUS-MONKEYS DURING ANTIPROGESTIN TREATMENT', ENDOCRINOLOGY, 132 1845-1856 (1993)
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1993 |
HIRST JJ, CHIBBAR R, MITCHELL BF, 'ROLE OF OXYTOCIN IN THE REGULATION OF UTERINE ACTIVITY DURING PREGNANCY AND IN THE INITIATION OF LABOR', SEMINARS IN REPRODUCTIVE ENDOCRINOLOGY, 11 219-233 (1993)
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1992 |
Hirst JJ, Haluska GJ, Cook MJ, Hess DI, Novy MJ, 'Comparison of plasma oxytocin and catecholamine concentrations with uterine activity in pregnant rhesus monkeys', Obstetrical and Gynecological Survey, 47 125-127 (1992)
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1992 |
Hirst JJ, West NB, Brenner RM, Novy MJ, 'Steroid hormone receptors in the adrenal glands of fetal and adult rhesus monkeys.', The Journal of Clinical Endocrinology & Metabolism, 75 308-314 (1992)
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1992 |
HIRST JJ, WEST NB, BRENNER RM, NOVY MJ, 'STEROID-HORMONE RECEPTORS IN THE ADRENAL-GLANDS OF FETAL AND ADULT RHESUS-MONKEYS', JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 75 308-314 (1992)
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1991 |
HIRST JJ, HALUSKA GJ, COOK MJ, HESS DL, NOVY MJ, 'COMPARISON OF PLASMA OXYTOCIN AND CATECHOLAMINE CONCENTRATIONS WITH UTERINE ACTIVITY IN PREGNANT RHESUS-MONKEYS', JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 73 804-810 (1991)
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1990 |
HIRST JJ, RICE GE, JENKIN G, THORBURN GD, 'REGULATION OF OXYTOCIN SECRETION BY THE OVINE CORPUS-LUTEUM - EFFECT OF ACTIVATORS OF PROTEIN KINASE-C', JOURNAL OF ENDOCRINOLOGY, 124 225-232 (1990)
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1988 |
HIRST JJ, RICE GE, JENKIN G, THORBURN GD, 'CONTROL OF OXYTOCIN SECRETION BY OVINE CORPORA-LUTEA - EFFECTS OF ARACHIDONIC-ACID, PHOSPHOLIPASES, AND PROSTAGLANDINS', ENDOCRINOLOGY, 122 774-781 (1988)
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1986 |
HIRST JJ, RICE GE, JENKIN G, THORBURN GD, 'SECRETION OF OXYTOCIN AND PROGESTERONE BY OVINE CORPORA-LUTEA INVITRO', BIOLOGY OF REPRODUCTION, 35 1106-1114 (1986)
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