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Dr Richard Yu


School of Environmental and Life Sciences (Environmental Science and Management)

A helping hand for fathers

A team leader within the Faculty of Health and Medicine's Family Action Centre, Dr Richard Fletcher is shining a spotlight on the role of fathers.

Dr Richard Fletcher 

Dr Richard Fletcher leads the Fathers and Families Research Program (FFRP) within the Family Action Centre at the University of Newcastle.

The FFRP team focus on research and teaching around fathers, particularly fathers of young children and babies.

Richard believes that we as a society need to change our expectations and beliefs relating to the role of fathers, for the benefit of the whole family and wider society.

Actively working towards this goal, Richard and his team have several projects in the works. They are in the process of trialing a smartphone based program that will offer information, mood assessment and support for new and expectant fathers, in a bid to identify and address paternal perinatal depression.

Another project, run by Dr Jennifer St George, is assessing the importance and safe limits of rough and tumble play between fathers and children, beginning with pre-school aged children.

A third project sees Dr Chris May working with couples on parenting partnerships. Through identifying and encouraging factors that create successful co-parenting dynamics, the projects aims to enhance the well-being of all members of the family.

As a result of the team's work, both government departments and non-government organisations (NGOs) have begun to review their policies and standard practices to identify and enhance opportunities for fathers' involvement.


As well as teaching courses in the Master in Family Studies program, the team provide consultancy services to organisations around Australia, and across the globe, on how to more successfully engage fathers in areas that have previously been dominated by maternal caregivers.

Richard sees the consultation work that he and the team at the Family Action Centre undertake with health professionals, and other services such as schools and welfare agencies, as a giant step towards changing understandings of the roles of fathers. But there is still a long way to go.

"There's still a very strong idea in the community and amongst professionals about parental roles. Many think that engaging mothers as the primary caregiver is sufficient, and fathers are just an optional extra," he explains.

"Fathers are invisible in many places, and that is endemic. Not because people dislike fathers, but because the system is set up to be focused on mothers."

Some services and organisations are aware of the need to engage dads, but have been unsuccessful in their attempts.

"When people are challenged about this, they generally want dads involved," Richard affirms.

"Often, however, they just don't know how to do it."


Richard's research revealed possible long-term negative impacts on the children of dads with mental health issues. Fathers' depressive symptoms in the first year after the birth predicted behavior problems in their children years later.

"If dads' mental health has such a dramatic impact then we need to be screening dads for depression, not just mums," Richard explains.

"This is a relatively new idea."

"We were so focused on the mum being the main affect that we didn't factor in the dads. Now we see it matters a lot, right from birth."

New costs related to babies, decreased family income due to maternal leave, plus new and extra family related duties, often combine to make the physical attendance of men at perinatal services impractical.

This increased pressure comes at a time where changes to routines and relationships can create stress and isolation, making dads vulnerable.

"We always worked on the idea that dad's should come to the same groups as the mums, parenting classes and things like that," he recalls.

"But then we thought, what if you weren't trying to do that, what if you accepted the fact that they're not able to come in, how do you talk to them?"


In response to these limitations, Richard and his team have designed a smart-phone based program that allows mobile connection for new and expectant dads.

Participants will receive texts containing information and links, and self-report their mood. If the mood tracker identifies them as needing extra support, they will be offered a phone call from a counsellor trained in this area.

Following the recent success of a six week pilot of the SMS4dads program, a twelve month trial will start later this year. Funding for the program, which includes a website and social media presence, comes from Beyond Blue and the Movember Foundation.

"When dad's miss the classes or activities, they miss the contact and the links to other people.  They may never get the chance to say to anyone, look I'm really stressed," he points out.

"This is a way of bringing dads into the system and keeping them hooked up," explains Richard.


Although only in the trial phase, the SMS4dads project has already produced spin-off programs.

Richard and his team are working with the Young and Well Co-operative Research Centre, local Aboriginal communities, and the University of Newcastle's Centre for Rural and Remote Mental Health to develop a website for young Aboriginal dads.

The Stayin' on Track: Young Aboriginal Fathers Project is focused on the experiences of young Aboriginal dads in Moree, Tamworth and Newcastle.

The project participants receive the same smartphone mood assessment and information as the SMS4Dads users, but also receive follow up support directly from community leaders and project facilitators, Charlie Faulkner and Craig Hammond.

A pivotal component of the project involves the participants sharing their stories. Filmed interviews with the fathers will be available on the website for other dads to access.

Another spin-off is in the works with the Queensland Department of Health.

"They were looking to run a project using SMS messages for mums. When they heard about our SMS for dads projects they approached us to partner with them," Richard explains.

"It's a much more mainstream approach so we're very excited about that." 


Richard credits a varied career, a talented and innovative team, and much life experience for affording him the insight needed to address the challenges related to actively engaging dads.

Following a stint as a high school science teacher, Richard took up to a position in the Equity Unit at the University of Newcastle.

From there his maths and teaching qualifications gained him a position in Holistic Health within the Faculty of Health.

After completing his masters in Medical Science, studying epidemiology, Richard earned his PhD focusing on fathers and attachment.

Although not a clinician himself, Richard often works with health professionals on issues related to fathers, and has delivered many antenatal programs for expectant dads.

He credits his own family with giving him the advanced understanding of the role of fathers needed to make his work relevant.

"I have three daughters and two stepdaughters,"

"My kids would say they taught me just about everything I know and they'd be right. They've taught me a lot, and still do."

Dr Richard Fletcher

A helping hand for fathers

Dr Richard Fletcher is building support systems for new fathers using text, internet and peer-designed video to deliver information to dads on their mobile ph

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Back to the future: Feedback control and favourable odds

Combating uncertainty with algorithm designs and computer simulations, Professor Rick Middleton's electrical engineering research is helping to improve the efficiency of a number of real-world processes.

Professor Rick Middleton 

Studying practical problems from a mathematical viewpoint isn't for everyone. For Middleton though, it's a satisfying challenge. His theoretical work involves 'a lot' of calculus, differential equations and linear algebra, and simultaneously (and surprisingly) adopts some of the creative thinking techniques usually reserved for those in the literary arts.

'My mind is quite analytical,' he admits.

 'But there are no clear-cut answers or solutions in the research I undertake.'

'Problems are always formulated as abstractions of reality with limited fixed steps and many possible directions.'

Adding to this unusual twist in investigative efforts, Middleton is ambitiously looking to optimise feedback control loops in a broad range of dynamic systems. The electrical engineer's multi-capacity algorithms are designed to regulate behaviours in industrial, biological and mechanical processes, with recognition of the need to combat – and sometimes just cope with – instability also influencing these adjustments.

'We're looking at things where the action you take now affects things over time,' he explains.

'So what we want to do is watch what happens a little further down the track, compare that with what we want to happen, and then modify control loops based on these observations.'

'If we knew everything and could predict the future perfectly we wouldn't need to bother.'

Computational complexities

Middleton first began exploring the creative constraints and opportunities of feedback mechanisms during his PhD candidateship in the late 80s. Opting to study computer control systems, the born and bred Novocastrian formulated differential equations to demonstrate the likenesses between analog integrated circuits and discrete time models.

'The two were once thought to be very different due to the way their mathematics had developed,' he says.

'But I was able to prove they're in fact quite close with one another.'

At the same time valuing the differences between discrete time models and analog integrated circuits, Middleton was also able to reformulate computer controls so that they took advantage of operational incongruences. With measurements and adjustments made at finite points in the former, and measurements and adjustments made continuously in the latter, he similarly showed uncertainties could be accounted for by meeting somewhere in the middle.  

'Instead of focusing purely on what happens next, which had long been the case for computer control systems, I used differences to indicate that we should really be looking at what happens between now and the next step,' Middleton discloses.

The pluck of the Irish

Seeking to build on this understanding of system dynamics post-PhD, Middleton initiated a number of projects in health sciences and other fields. Working both here and abroad during these earlier research days, he also sought to expand the application of feedback control loops.

'Early efforts in feedback control involved electronic amplifiers,' the Institute of Electrical and Electronics Engineers Fellow explains.

'At the time they had very good gain properties but would often add extra harmonics, which distorted the sound.'

'Feedback mechanisms were engineered to ensure nothing had to be compromised – the signal could be boosted to make it louder without any distortion.'

Another of Middleton's projects involved studying systems biology – this time in the Republic of Ireland. He took on a five-year appointment at the National University of Ireland Maynooth's Hamilton Institute, electing to approach the behaviour and dynamics of Parkinson's Disease from a novel mathematical angle.  

'What happens in patients with Parkinson's is quite well studied in terms of the sequence of events, but it's not well understood in terms of what causes what,' Middleton concedes.

'We don't know exactly why the neurons degenerate.'

Recognising the 'reasonably large impact' Parkinson's has on our aging society, the Director of the University of Newcastle's Centre for Complex Dynamic Systems and Control also sought to understand how the disease progresses despite common drugs used that compensate for the symptoms resulting from dopamine losses.

'We looked at particular cells in the brain, especially some of the neurons that degenerate early,' he says.

'We also looked at the different feedback mechanisms that exist there and why things might go wrong and cause damage to these cells.'

Fine-tuning the green machine

Most recently, Middleton has been researching and revising renewable energy processes. He's collaborating with a PhD candidate, Sonja Stuedli, to examine the current behaviours of electricity suppliers and consumers.

'At the moment it's reasonably cheap to produce renewable energy but often hard for us to store – and this is well known,' Middleton asserts.

'Renewables can be stored very effectively in hydro systems but we don't have enough of these systems to store the amount we need.'

Simultaneously conducting mathematical analyses and computer simulations of local load capacities, the pair is also looking to ensure homeowners are able to make the most of available energy resources. Sometimes things as simple as having signals from a central authority to let us know when there's too much power being used or there's some spare, these adjustments take full advantage of the rapidly varying generation of renewables.

'One of the other things people have realised is that if we were smarter in our homes about being able to turn things on and off and reduce our load at the right time, we could match up our consumption of energy to when cheap energy is readily accessible,' he declares.

'This will allow us to match up demand with solar sources without the big demand for storage.'

Providing feedback on feedback

Acknowledging the study of single feedback loops is now 'largely done,' Middleton anticipates a shift in the direction of Control Theory research. Already talking about expanding smart grids and introducing smart cities, the multiple-award winner also points to a fundamental reengineering of electrical and telecommunications industries.  

'Almost all of the problems we continue to have, even little things like finding a car parking spot at University, tend to worry about the dynamics and the effect of the answer,' he says.

'In many ways feedback control could and should help us to manage these intricacies and uncertainties.'

Professor Rick Middleton

Back to the future: Feedback control and favourable odds

Professor Rick Middleton is Director of the Priority Research Centre for Dynamic Systems and Control. His theoretical work is primarily focused on Control and

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Collaborative Environments for Creative Arts Research

Collaborative Environments for Creative Arts Research (CeCAR) is a newly launched research group within the Faculty of Education and Arts at The University of Newcastle.

CeCAR brings together national and international researchers in the creative arts, humanities, sciences, health and social sciences with external collaborators in the community, industry, other universities and institutes.

CeCAR Director, Professor Richard Vella, said CeCAR provides an interface for artists outside the university to collaborate with researchers in the creative arts, sciences, social sciences, humanities and health.

"From an interdisciplinary perspective, expertise from diverse disciplines combined with the creative arts can produce new outputs and models of understanding in the science, technology and humanities disciplines. They can also generate exciting new art works based on this research, "Professor Vella said.

"Research in haptics, interactivity, digital environments, robotics, communication and cognition are just some examples of fields that can include creative arts research."

Two successful projects already undertaken by CeCAR include:

  • Supanova, a rich media peer review annotation software environment for the presentation and discussion of research in the creative arts.
  • The Space Time Concerto competition featuring an internet-linked ensemble spanning five countries.

For more information visit CeCAR.

Collaborative Environments for Creative Arts Research

Collaborative Environments for Creative Arts Research (CeCAR) is a newly launched research group within the Faculty of Education and Arts

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Career Summary


I received my PhD from City University of Hong Kong in 2002. After my postdoctoral training with Prof. Rudolf Wu, I continued to work in the same institution as a Lecturer until joining the University of Newcastle in 2009. I am now an academic in the Discipline of Environmental Science and Management in the School of Environmental & Life Sciences (SELS).

My primary research interests are in the Molecular Toxicology of Environmental Stressors and Chemicals.

In particular, I am interested in (1) understanding the molecular mechanisms of endocrine disruption caused by hypoxia and environmental chemicals and (2) developing cell- and animal-based assays for the screening and detection of endocrine-disrupting chemicals (EDCs). Overall, my research covers both basic science aimed at understanding the fundamental mechanisms of environmental toxicity and applied science concerned with the development of diagnostic tools for assessing and monitoring environmental toxicity. Outlined below is a summary of my recent research activities and findings:   

1. Environmental Obesogens

The prevalence of obesity has been dramatically increasing worldwide during the last several decades. In recent years, there is growing epidemiological evidence indicating a positive correlation between the exposure of human population to EDCs and body weight, suggesting a possible role of EDCs in increasing obesity rates. The "obesogen hypothesis" is an emerging view proposing that exposure to a subset of these chemicals (obesogens) disrupts the weight-control mechanisms and ultimately increases obesity. To date, most of the known obesogens are those directly increasing adipogenesis and lipid accumulation, while the ones that contribute to diet-induced obesity (DIO) are understudied.

Leptin is an adipocyte-derived hormone that represses appetite and increases energy expenditure. Leptin inhibits appetite by decreasing the activity of the orexigenic NPY/AgRP/GABA neurons and increasing the activity of the anorexigenic POMC/CART neurons in the hypothalamus. Leptin action is exerted through its binding to the leptin receptor (OB-R) expressed on the surface of these neurons. Recent research showed that the disruption of OB-R activation (after treatment with leptin antagonists) during early development can lead to adult leptin resistance. Leptin resistance is a medical condition in which individuals are weakly responsive or unresponsive to high circulating levels of leptin and regarded as an important predisposing factor for DIO. Based on this existing knowledge, we hypothesise that early-life exposure to environmental chemicals that act as leptin antagonists can enhance the development of leptin-resistance and DIO in adults.  

In collaboration with my co-worker Dr Richard Kong at City University of Hong Kong, a pilot screening program was recently initiated to identify environmental chemicals that act as leptin antagonists using biophysical and cell-based assays. Further effort will be made to assess the ability of the identified candidates to induce the developmental programming of adult leptin resistance and DIO using zebrafish (an important human disease model). This project is anticipated to provide important information regarding the contribution of developmental programming to the obesity epidemic, through assessing the role of early-life exposure of environmental chemicals in the development of adult leptin resistance and obesity. Since the rising prevalence of obesity has been recently noticed in livestock, pets, and wild animals, the knowledge about the mechanism of action of environmental obesogens and the technologies developed in this research could also be applied to a much broader range of biota beyond humans. Eventually, the outcome of this research may aid in devising new regulations on the safety of animal feed and the release of obesogenic chemicals to the environment.

2. Estrogen-mediated Vitellogenesis in Oysters

Oysters respond to EDC mixtures with the induction of the female egg yolk protein, vitellogenin (Vtg), availing a biomarker which indicates the presence of estrogenic contaminants in sewage effluent receiving waters. Despite this, the precise mechanism through which estrogens exert their action to induce vitellogenesis is unknown. Estrogen receptors (ERs) with homology to vertebrate ERs have been identified in selected molluscan taxa, yet those found to date do not bind or are unresponsive to estrogen. We hypothesise that estrogens may bind to receptors yet to be identified in Mollusca, with lower structural similarity to vertebrate-like ERs, and such receptors act as estrogen-dependent transcriptional regulators of vitellogenin expression. In an effort to investigate this possibility, Dr Geoff MacFarlane (UoN) and I initiated a project to isolate and characterise novel “functional” ERs from the native Sydney rock oyster (Saccostrea glomerata). Our recent progress indicated that an invertebrate-like ER isolated from the Sydney rock oyster ovarian tissues shares a similar ligand (estrogen) binding pocket with that of the human ER and is expressed in response to estrogenic compounds. Further effort will be directed at clarifying its functional roles in mediating vitellogenesis and gonadal development and its epigenetic regulation in response to the exposure to estrogenic compounds. At the application level, this research will provide important information (an ER pathway specific to invertebrates) for the development of bioassays for screening xenoestrogens with ecotoxicological relevance to molluscs.

3. Fish Hypoxia

Previously, my co-workers and I have demonstrated for the first time that hypoxia can disrupt sex differentiation via modulation of gene expression for estrogen biosynthesis, leading to a male-biased sex ratio in zebrafish (Shang et al. 2006). This work has highlighted the alarming impacts of aquatic hypoxia on fish reproduction and sustainability, and thus attracted worldwide attention, as exemplified by cover stories written by Science and Nature as well as reports by CNN and ABC. This study has been cited 60 times since its publication in 2006. Later studies also provided scientific evidence that the transcription factor hypoxia-inducible factor-1 (HIF-1) regulates a number of genes involved in fish growth and reproduction in response to hypoxia (Yu et al. 2006a, 2008; Chu et al. 2010). To assess the applicability and specificity of HIF-1-regulated gene expression as biomarkers for monitoring aquatic hypoxia, we also made efforts to decipher the crosstalk between the xenobiotic transformation pathway and the HIF-1 pathway. Intriguingly, we demonstrated that the existence of xenobiotics can enhance HIF-1-mediated gene expression via increasing the cellular levels of reactive oxygen species (ROS), indicating that the presence of environmental xenobiotics must be considered when interpreting HIF-1-based hypoxia biomarker results (Yu et al. 2008). In 2012, my co-workers (Kong & Wu) and I obtained a seed fund ($US 115,384) from the State Key Laboratory in Marine Pollution, China to study the interactive effects of climate change and hypoxia on fish sex determination. 

4. Fish Leptin

The study of obesity and appetite control in fish models is an emerging field of research. In the last few years, my co-workers and I highlighted striking similarities in the function and regulation of leptin between fish and mammals. Our recent work suggests that leptin elevation under hypoxic conditions is a pathophysiological response common to both zebrafish and mammalian models (Chu et al. 2010). In another prior study, we reported for the first time the characterization of a fish long-form leptin receptor that contains all the signature motifs and domains found in the mammalian leptin receptors (Wong, Yu et al. 2007), implying the function of leptin receptor is conserved in both fish and mammals. Recently, using gain-or-loss gene function techniques, we demonstrated that leptin is the molecular link between hypoxia and endocrine disruption, leading to the suppression of the aromatase gene (cyp19a) and hence estrogen production in fish (Yu et al. 2012). Taken together, these findings provide novel insights into the molecular mechanism of endocrine disruption under hypoxia. This research successfully attracted $US 108,974 funding from Hong Kong General Research Fund (GRF) in 2011.

5. In-vitro bioassays for EDCs

For years, I have been collaborating with Prof. John Giesy (Canada Research Chair in Environmental Toxicology, University of Saskatchewan) on the development and validation of a H295R cell line screening test to evaluate toxicant-induced effects on steroid biosynthesis (steroidogenesis)—the H295R Steroidogenesis Assay (Gracia et al. 2004; Zhang et al. 2005; Gracia et al. 2006; Xu et al. 2006; Gracia et al. 2007; He et al. 2008; Song et al. 2008). This assay has been successfully used to assess the endocrine-disrupting potential and the mechanisms of action of various chemicals and environmental samples. This assay is currently being developed as part of Tier 1 of the US EPA Endocrine Disruptor Screening Program and an Organization for Economic Cooperation and Development (OECD) test method validation program.

6. In-vivo bioassays for EDCs

We recently demonstrated that induction of hepatic choriogenin H (ChgH, a fish egg-shell protein precursor) mRNA expression in male marine medaka can serve as a highly sensitive biomarker for environmental estrogens (its sensitivity is even better than vitellogenin) (Yu et al. 2006b; Cheng et al. 2008). This novel discovery led us to develop a ChgH-GFP transgenic marine medaka for monitoring environmental estrogens in marine water. Our recent progress indicated that this sentinel fish can detect 17β-estradiol (E2) at nominal concentrations as low as 1 μg/L. To make quantification of in vivo GFP expressed in developing fish embryos feasible, we previously developed an automatic 4D (3D plus time) acquisition system and the imaging processes of deconvolution and thresholding (Yu et al. 2006c). This 4D imaging system provides a simple but powerful means to quantify in vivo gene expression in a developmental toxicology context. The technologies have been successfully commercialised as environmental and food safety consultancy service in Hong Kong (Vitargent (International) Biotechnology Ltd). 

Research Expertise
Ecotoxicology Molecular toxicology Obesogen screening Embryotoxicity assays Development of bioassays for EDC screening and detection

Teaching Expertise
BIOL1003 Professional Skills for Biological Sciences 1 BIOL2070 Ecology ENVS3004 Ecotoxicology

Administrative Expertise
BSc Merit Pathway Convenor Deputy Program Convenor - B. Environmental Science & Management (Honours)

For years, I have been working in close collaboration with Prof Rudolf Wu (University of Hong Kong), Dr Richard Kong (City University of Hong Kong) and Prof John Giesy (University of Saskatchewan) on hypoxia and EDC research. Recent collaborative projects (funded) include: 1. CityU Seed Grant, City University of Hong Kong – 2013 (Project no. 7003027) Investigators: A/P Richard Kong, Dr Richard Yu Title: Pilot study to identify environmental obesogens (chemicals that cause overeating) using BRET (Bioluminescence Resonance Energy Transfer) and cell-based assays Funding: $US 12,821 2. State Key Laboratory in Marine Pollution, China – 2012 (Project no. 9369101) Investigators: A/P Richard Kong, Prof Rudolf Wu, Dr Richard Yu Project Title: Interactive effects of climate change and hypoxia on fish sex determination: estrogen synthesis and masculinisation Funding: $US 115,384 3. General Research Fund, Hong Kong Research Grants Council – 2011 (Project no. 160411) Investigators: A/P Richard Kong, Prof John Giesy, Dr Richard Yu Project Title: Uncovering the molecular links between hypoxia and endocrine disruption: A functional study of zebrafish leptin Funding: $US 108,974


  • PhD, City University of Hong Kong - China
  • Bachelor of Science (Applied Biology)(Honours), City University of Hong Kong - China


  • EDC
  • Endocrine disrupting chemicals
  • Environmental estrogens
  • Fish
  • Hypoxia
  • Molecular Toxicology
  • Obesogens
  • Sydney rock oyster

Fields of Research

Code Description Percentage
050199 Ecological Applications not elsewhere classified 20
060199 Biochemistry and Cell Biology not elsewhere classified 40
111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified 40

Professional Experience

UON Appointment

Title Organisation / Department
Lecturer University of Newcastle
School of Environmental and Life Sciences


For publications that are currently unpublished or in-press, details are shown in italics.

Journal article (28 outputs)

Year Citation Altmetrics Link
2015 Yu RMK, Chaturvedi G, Tong SKH, Nusrin S, Giesy JP, Wu RSS, Kong RYC, 'Evidence for microRNA-mediated regulation of steroidogenesis by hypoxia', Environmental Science and Technology, 49 1138-1147 (2015)

Environmental hypoxia can occur in both natural and occupational environments. Over the recent years, the ability of hypoxia to cause endocrine disruption via perturbations in ste... [more]

Environmental hypoxia can occur in both natural and occupational environments. Over the recent years, the ability of hypoxia to cause endocrine disruption via perturbations in steroid synthesis (steroidogenesis) has become increasingly clear. To further understand the molecular mechanism underlying hypoxia-induced endocrine disruption, the steroidproducing human cell line H295R was used to identify microRNAs (miRNAs) affecting steroidogenic gene expression under hypoxia. Hypoxic treatment of H295R cells resulted in the downregulation of seven steroidogenic genes and one of these, CYP19A1 (aromatase), was shown to be regulated by the transcription factor hypoxia-inducible factor-1 (HIF-1). Using bioinformatic and luciferase reporter analyses, miR-98 was identified to be a CYP19A1- targeting miRNA from a subset of HIF-1-inducible miRNAs. Gain- and loss-of-function analysis suggested that under hypoxia, the increased expression of miR-98 led to the downregulation of CYP19A1 mRNA and protein expression and that it may have contributed to a reduction in estradiol (E2) production. Intriguingly, luciferase reporter assays using deletion constructs of a proximal 5'-flanking region of miR-98 did not reveal a hypoxia-responsive element (HRE)-containing promoter. Overall, this study provided evidence for the role of miRNAs in regulating steroidogenesis and novel insights into the molecular mechanisms of hypoxia-induced endocrine disruption. (Figure Presented).

DOI 10.1021/es504676s
2014 Lu X, Yu RMK, Murphy MB, Lau K, Wu RSS, 'Hypoxia disrupts gene modulation along the brain-pituitary-gonad (BPG)-liver axis', Ecotoxicology and Environmental Safety, 102 70-78 (2014) [C1]

Hypoxia alters sex hormone concentrations leading to reproductive impairment in fish; however the mechanisms underlying these effects remain largely unknown. Using zebrafish (Dani... [more]

Hypoxia alters sex hormone concentrations leading to reproductive impairment in fish; however the mechanisms underlying these effects remain largely unknown. Using zebrafish (Danio rerio), this study is the first to demonstrate that hypoxia causes endocrine disruption by simultaneously acting on multiple targets along the brain-pituitary-gonadal (BPG)-liver axis in fish. Alterations in the expression of key genes associated with reproductive endocrine pathways in the brain (sGnRH), pituitary (FSHß and LHß), gonads (FSH-R, LH-R, HMGR, StAR, CYP19A, CYP11A, CYP11ß and 20ß-HSD), and liver were correlated with significant reductions of estradiol in females and testosterone in males. Hypoxia also induced sex-specific and tissue-specific changes in the expression of estrogen, androgen, and membrane progestin receptors along the BPG axis, suggesting disruption of the feedback and synchronization of hormone signals. Furthermore, the hypoxia-induced upregulation of hepatic sex hormone-binding globulin suggests an increase in hormone transport and reduced bioavailability in blood, while upregulation of hepatic CYP3A65 and CYP1A in females suggests an increase in estrogen biotransformation and clearance. Given that the regulation of reproductive hormones and the BPG-liver axis are highly conserved, this study provides new insights into the hypoxia-induced endocrine disrupting mechanisms and reproductive impairment in other vertebrates. © 2014 Elsevier Inc.

DOI 10.1016/j.ecoenv.2014.01.017
Citations Scopus - 4
2012 Yu MKR, Chu DLH, Tan T-F, Li VWT, Chan AKY, Giesy JP, et al., 'Leptin-mediated modulation of steroidogenic gene expression in hypoxic zebrafish embryos: Implications for the disruption of sex steroids', Environmental Science & Technology, 46 9112-9119 (2012) [C1]
Citations Scopus - 8Web of Science - 8
2011 Lo KH, Hui MNYH, Yu MKR, Wu RSS, Cheng SH, 'Hypoxia impairs primordial germ cell migration in zebrafish (danio rerio) embryos', PLoS ONE, 6 e24540 (2011) [C1]
Citations Scopus - 10Web of Science - 9
2010 Chu DLH, Li VWT, Yu MKR, 'Leptin: Clue to poor appetite in oxygen-starved fish', Molecular and Cellular Endocrinology, 319 143-146 (2010) [C1]
DOI 10.1016/j.mce.2010.01.018
Citations Scopus - 17Web of Science - 17
2010 Ng PKS, Yu MKR, Kwong TFN, Wong MML, Kong RYC, 'Transcriptional regulation and functional implication of the grass carp CITED1 (gcCITED1) in the negative regulation of HIF-1', International Journal of Biochemistry and Cell Biology, 42 1544-1552 (2010) [C1]
DOI 10.1016/j.biocel.2010.06.007
Citations Scopus - 2Web of Science - 2
2009 Ng PKS, Chiu S-K, Kwong TFN, Yu MKR, Wong MML, Kong RYC, 'Functional characterization of two CITED3 homologs (gcCITED3a and gcCITED3b) in the hypoxia-tolerant grass carp, Ctenopharyngodon idellus', BMC Molecular Biology, 10 1-14 (2009) [C1]
DOI 10.1186/1471-2199-10-101
Citations Scopus - 3Web of Science - 2
2009 Zhou HW, Wong AHY, Yu RMK, Park YD, Wong YS, Tam NFY, 'Polycyclic Aromatic Hydrocarbon-Induced Structural Shift of Bacterial Communities in Mangrove Sediment', MICROBIAL ECOLOGY, 58 153-160 (2009) [C1]
DOI 10.1007/s00248-008-9456-x
Citations Scopus - 33Web of Science - 28
2008 Song R, He Y, Murphy MB, Yeung LWY, Yu RMK, Lam MHW, et al., 'Effects of fifteen PBDE metabolites, DE71, DE79 and TBBPA on steroidgenesis in the H295R cell line', Chemosphere, 71 1888-1894 (2008) [C1]
DOI 10.1016/j.chemosphere.2008.01.032
Citations Scopus - 31Web of Science - 30
2008 Chen X, Li VWT, Yu RMK, Cheng SH, 'Choriogenin mRNA as a sensitive molecular biomarker for estrogenic chemicals in developing brackish medaka (Oryzias melastigma)', Ecotoxicology and Environmental Safety, 71 200-208 (2008) [C1]
DOI 10.1016/j.ecoenv.2007.10.005
Citations Scopus - 16Web of Science - 16
2008 Yu RMK, Ng PKS, Tan T, Chu DLH, Wu RSS, Kong RYC, 'Enhancement of hypoxia-induced gene expression in fish liver by the aryl hydrocarbon receptor (AhR) ligand, benzo[a]pyrene (BaP)', Aquatic Toxicology, 90 235-242 (2008) [C1]
DOI 10.1016/j.aquatox.2008.09.004
Citations Scopus - 14Web of Science - 15
2008 He Y, Murphy MB, Yu RMK, Lam MHW, Hecker M, Gisey JP, et al., 'Effects of twenty PBDE metabolites on steroidgenesis in the H295R cell line', Toxicology Letters, 176 230-238 (2008) [C1]
DOI 10.1016/j.toxlet.2007.12.001
Citations Scopus - 69Web of Science - 67
2007 Kong RYC, Law SHL, Chu JKY, Ng PKD, Yu RMK, Wu RSS, 'Functional and molecular plasticity of the HIF transcription factors', COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY, 148 S7-S7 (2007)
DOI 10.1016/j.cbpa.2007.06.016
2007 Shang EHH, Yu RMK, Wu RSS, 'Hypoxia alters sex hormones, sex ratio and favors a male-dominated population in fish', COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY, 148 S118-S118 (2007)
DOI 10.1016/j.cbpa.2007.06.294
Citations Web of Science - 1
2007 Chen X, Kinoshita M, Hirata T, Yu RMK, Cheng SH, 'Transgenic marine medaka (Oryzias melastigma): a sensitive sentinel for estrogenic pollutants', MOLECULAR & CELLULAR TOXICOLOGY, 3 34-34 (2007)
Citations Web of Science - 8
2007 Wong MML, Yu RMK, Ng PKS, Law SHW, Tsang AKC, Kong RYC, 'Characterization of a hypoxia-responsive leptin receptor (omLepR(L)) cDNA from the marine medaka (Oryzias melastigma)', MARINE POLLUTION BULLETIN, 54 797-803 (2007) [C1]
DOI 10.1016/j.marpolbul.2007.01.025
Citations Web of Science - 24
2007 Gracia T, Hilscherova K, Jones PD, Newsted JL, Higley EB, Zhang X, et al., 'Modulation of steroidogenic gene expression and hormone production of H295R cells by pharmaceuticals and other environmentally active compounds', TOXICOLOGY AND APPLIED PHARMACOLOGY, 225 142-153 (2007) [C1]
DOI 10.1016/j.taap.2007.07.013
Citations Web of Science - 28
2006 Xu Y, Yu RMK, Zhang XW, Murphy MB, Giesy JP, Lam MHW, et al., 'Effects of PCBs and MeSO2-PCBs on adrenocortical steroidogenesis in H295R human adrenocortical carcinoma cells', CHEMOSPHERE, 63 772-784 (2006) [C1]
DOI 10.1016/j.chemosphere.2005.08.013
Citations Web of Science - 30
2006 Yu RMK, Lin CC, Chan PK, Chow ESH, Murphy MB, Chan BP, et al., 'Four-dimensional imaging and quantification of gene expression in early developing zebrafish (Danio rerio) embryos', TOXICOLOGICAL SCIENCES, 90 529-538 (2006) [C1]
DOI 10.1093/toxsci/kfj115
Citations Web of Science - 10
2006 Gracia T, Hilscherova K, Jones PD, Newsted JL, Zhang X, Hecker M, et al., 'The H295R system for evaluation of endocrine-disrupting effects', ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY, 65 293-305 (2006) [C1]
DOI 10.1016/j.ecoenv.2006.06.012
Citations Web of Science - 49
2006 Yu RMK, Wong MML, Kong RYC, Wu RSS, Cheng SH, 'Induction of hepatic choriogenin mRNA expression in male marine medaka: A highly sensitive biomarker for environmental estrogens', AQUATIC TOXICOLOGY, 77 348-358 (2006) [C1]
DOI 10.1016/j.aquatox.2006.01.003
Citations Web of Science - 22
2006 Law SHW, Wu RSS, Ng PKS, Yu RMK, Kong RYC, 'Cloning and expression analysis of two distinct HIF-alpha isoforms - gcHIF-1alpha and gcHIF-4alpha - from the hypoxia-tolerant grass carp, Ctenopharyngodon idellus', BMC MOLECULAR BIOLOGY, 7 (2006) [C1]
DOI 10.1186/1471-2199-7-15
Citations Web of Science - 42
2006 Yu RMK, Chen EXH, Kong RYC, Ng PKS, Mok HOL, Au DWT, 'Hypoxia induces telomerase reverse transcriptase (TERT) gene expression in non-tumor fish tissues in vivo: The marine medaka (Oryzias melastigma) model', BMC Molecular Biology, 7 (2006) [C1]
DOI 10.1186/1471-2199-7-27
2006 Shang EHH, Yu RMK, Wu RSS, 'Hypoxia affects sex differentiation and development, leading to a male-dominated population in zebrafish (Danio rerio)', ENVIRONMENTAL SCIENCE & TECHNOLOGY, 40 3118-3122 (2006) [C1]
DOI 10.1021/es0522579
Citations Web of Science - 103
2005 Zhang XW, Yu RMK, Jones PD, Lam GKW, Newsted JL, Gracia T, et al., 'Quantitative RT-PCR methods for evaluating toxicant-induced effects on steroidogenesis using the H295R cell line', ENVIRONMENTAL SCIENCE & TECHNOLOGY, 39 2777-2785 (2005) [C1]
DOI 10.1021/es048679k
Citations Web of Science - 59
2005 Yu RMK, Wong MML, Jack RW, Kong RYC, 'Structure, evolution and expression of a second subfamily of protein phosphatase 2A catalytic subunit genes in the rice plant (Oryza sativa L.)', PLANTA, 222 757-768 (2005) [C1]
DOI 10.1007/s00425-005-0018-x
Citations Web of Science - 7
2004 Hilscherova K, Jones PD, Gracia T, Newsted JL, Zhang XW, Sanderson JT, et al., 'Assessment of the effects of chemicals on the expression of ten steroidogenic genes in the H295R cell line using real-time PCR', TOXICOLOGICAL SCIENCES, 81 78-89 (2004) [C1]
DOI 10.1093/toxsci/kfh191
Citations Web of Science - 96
2003 Yu RMK, Zhou Y, Xu ZF, Chye ML, Kong RYC, 'Two genes encoding protein phosphatase 2A catalytic subunits are differentially expressed in rice', PLANT MOLECULAR BIOLOGY, 51 295-311 (2003) [C1]
DOI 10.1023/A:1022006023273
Citations Web of Science - 14
Show 25 more journal articles

Conference (3 outputs)

Year Citation Altmetrics Link
2010 Priestley MN, Dunstan RH, O'Connor W, Van Zweiten R, Yu MKR, Macfarlane GR, 'Molluscan bio-monitor for quantification and impcat assessment of estrogenically active compounds in Australian marine ecosystems', 20th SETAC Europe Annual Meeting, Seville, Spain: Science and Technology Environmental Protection: Programme Book, Seville, Spain (2010) [E3]
Co-authors Geoff Macfarlane, Hugh Dunstan
2010 Yu MKR, Chu DLH, Li VWT, 'Leptin: A molecular link between hypoxia and endocrine disruption in fish?', 6th International Conference on Marine Pollution and Ecotoxicology. Programme & Abstracts, Hong Kong (2010) [E3]
2009 Yu MKR, 'Leptin: A molecular link between hypoxia and endocrine disruption in fish?', 13th Australasian Society for Ecotoxicology Conference: Posters, Adelaide, SA (2009) [E3]

Grants and Funding


Number of grants 2
Total funding $18,500

Click on a grant title below to expand the full details for that specific grant.

20121 grants / $13,500

Molecular mechanisms underpinning the induction of fish sex change by climate change stressors$13,500

Funding body: University of Newcastle - Faculty of Science & IT

Funding body University of Newcastle - Faculty of Science & IT
Project Team Doctor Richard Yu
Scheme Strategic Small Grant
Role Lead
Funding Start 2012
Funding Finish 2012
GNo G1401107
Type Of Funding Internal
Category INTE

20091 grants / $5,000

Role of leptin in hypoxia-induced inhibition of sterodogenesis in zebrafish embryos$5,000

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Doctor Richard Yu
Scheme New Staff Grant
Role Lead
Funding Start 2009
Funding Finish 2009
GNo G0189969
Type Of Funding Internal
Category INTE

Research Supervision

Current Supervision

Commenced Research Title / Program / Supervisor Type
2014 Ecotoxicology of Metals in Estuarine Invertebrates
Environmental Studies, Faculty of Science and Information Technology
Principal Supervisor
2012 Investigation of the Molecular Mechanisms Underlying Chemical-induced Endocrine Disruption in Sydney Rock Oysters (Saccostrea glomerata)
Environmental Studies, Faculty of Science and Information Technology
Principal Supervisor
2009 Discovering the Mechanisms of Estrogen Mediated Vitellogenesis in the Sydney Rock Oyster, Saccostrea Glomerata
Biological Sciences, Faculty of Science and Information Technology

Dr Richard Yu


Environmental Water Science Group
School of Environmental and Life Sciences
Faculty of Science and Information Technology

Focus area

Environmental Science and Management

Contact Details

Phone (02) 4921 6990
Fax (02) 4921 8977


Room LS2-45
Building Life Sciences
Location Callaghan
University Drive
Callaghan, NSW 2308