ESA-SRB-AOTA 2019

Ontogeny of polycystic ovary syndrome (PCOS) traits in a PCOS mouse model (#726)

Valentina Rodriguez Paris 1 , Melissa C Edwards 1 2 , Ali Aflatounian 1 , William L Ledger 1 , Robert B Gilchrist 1 , David J Handelsman 2 , Kirsty A Walters 1 2
  1. School of Women's & Children's Health, University of New South Wales, Sydney, NSW 2052, Australia
  2. ANZAC Research Institute, University of Sydney , Sydney, NSW 2139, Australia

Polycystic ovary syndrome (PCOS) affects 5-10% of women worldwide and is a complex disorder characterized by reproductive, endocrine and metabolic abnormalities. The aetiology and ontogeny of PCOS are poorly understood and therefore current medical management relies solely on symptomatic treatment. Defining the ontogeny of PCOS traits is important for early PCOS detection and treatment of this disorder. Hyperandrogenism is a defining characteristic of PCOS and clinical and animal studies support a role for androgen driven actions in the development of PCOS. Therefore, to determine the temporal and spatial pattern of PCOS trait development, we implanted mice with either a blank or a dihydrotestosterone (DHT) pellet at 4 weeks of age and evaluated PCOS features after 2, 4 and 8 weeks of androgen exposure. Compared to control mice, all androgen-exposed mice exhibited complete estrous acyclicity at all time-points (P<0.001), accompanied by anovulation as none of their ovaries exhibited corpora lutea. Large antral follicle populations were significantly increased in the 4 and 8 week DHT-exposed ovaries compared to controls (P<0.05). Body weight was significantly increased in androgen-exposed mice compared to controls at all time-points (P<0.001), with a significant increase in parametrial and retroperitoneal fat pad weight observed in the 8 week androgen-exposed group (P<0.001). Glucose tolerance was not impaired in any DHT-exposed mice compared to controls. However, basal glucose in the 8 week DHT-exposed females was significantly increased compared to control females (P<0.05), indicating development of the initial stage of hyperglycaemia that precedes type-2 diabetes. These results indicate that in the development of hyperandrogenic PCOS features, disrupted reproductive function and increased body weight precede the occurrence of additional PCOS related metabolic disturbances. These findings infer that altered reproductive function and weight gain are early indicators of PCOS, and may be key initial treatment targets to prevent or reduce the severity of PCOS.