Biological origins, aetiology and pathology of PCOS

The CRE in PCOS New Knowledge topic ‘Biological origins, aetiology and pathology of PCOS’ currently has four projects, as led by Professor Raymond Rodgers:
  • Fetal and pregnancy contributions
  • Pre and postnatal impact of androgen excess in PCOS
  • Pre and Intrapartum pregnancy factors
  • Impact and mechanisms of adiposity

If you would like further information about a research topic please contact the project lead.

biological origins

Fetal and pregnancy contributions

This research team has developed a new hypothesis on the role of specific genes in PCOS (particularly for fibrillin and transforming growth-factor proteins) interacting with the fetal ovary and linking fetal origins to reproductive and metabolic dysfunction. Testing this in current NHMRC-funded animal models is taking place. The CRE will extend this to examine other animal models and human tissues from funded PCOS studies.

Project Lead: Professor Raymond Rodgers

Pre and postnatal impact of androgen excess in PCOS

PCOS origins will be examined using unique, conditional, androgen receptor knockout mice (receptors inactivated in whole ovary, granulosa cells, hypothalamus) with pre- and postnatal PCOS mouse models enabling new mechanistic studies that cannot be replicated in humans. Under the CRE we will link clinical and lab research, and study additional mechanisms relevant in human PCOS studies (such as chronic inflammation and sympathetic nervous system activity) in these animal models.

Project Lead: Dr Kirsty Walters

Pre and Intrapartum pregnancy factors

This project will expand research on the impact of pre and intra-pregnancy factors (such as hyperandrogenism, maternal obesity, insulin resistance) on development of PCOS and subsequent reproductive, metabolic and psychological complications through our cohort studies. This project will also analyse androgens using mass spectrometry in the Raine and LIMIT cohorts.

Project Lead: Dr Lisa Moran

Impact and mechanisms of adiposity

Adiposity has a bidirectional relationship in PCOS. Women with PCOS are predisposed to weight gain, which in turn increases PCOS prevalence and severity. PCOS is underpinned by intrinsic insulin resistance, exacerbated by extrinsic obesity-related insulin resistance and responds to lifestyle changes. We are exploring the mechanisms of insulin resistance and obesity – including appetite regulation, dietary intake, exercise, sedentary behaviour, thermogenesis, mitochondrial function, inflammation, sympathetic dysfunction and adipokines. Using the cohorts and data pooled under the CRE from new and ongoing clinical trials in PCOS, this project will study natural history, antecedents, modulators, mechanisms and health impacts of obesity and IR in PCOS, including in Indigenous women. This project will also use sophisticated steroid profiling to elucidate the interactions between adiposity and androgens.

Project Lead: Professor Helena Teede