Oral Presentation ESA-SRB-AOTA 2019

The efficacy of dietary interventions in amending polycystic ovary syndrome (PCOS) traits in a PCOS mouse model     (#30)

Valentina Rodriguez Paris 1 , Samantha M Solon-Biet 2 , Alistair M Senior 2 , Melissa C Edwards 1 3 , Madeleine J Cox 1 , William L Ledger 1 , Robert B Gilchrist 1 , Stephen J Simpson 2 , David J Handelsman 3 , Kirsty A Walters 1 3
  1. School of Women's & Children's Health, University of New South Wales, Sydney, NSW 2052, Australia
  2. Charles Perkins Centre, University of Sydney , Sydney, NSW 2006, Australia
  3. ANZAC Research Institute, University of Sydney , Sydney, NSW 2139, Australia

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder featuring reproductive, endocrine and metabolic abnormalities. Its aetiology is unknown and current medical management is symptom based. Hyperandrogenism is a key characteristic of PCOS, and diet is innately associated as obesity is present in 40-80% of PCOS patients. Dietary interventions are a potentially powerful drug-free treatment to ameliorate PCOS manifestation, but the optimum diet for PCOS remains undetermined. We provided our dihydrotestosterone (DHT)-induced PCOS and control mice with ad libitum access to one of 10 diets varying in protein (P), carbohydrate (C) and fat (F) content, to determine the impact of dietary macronutrient balance on the development of PCOS features. All control mice cycled, while most PCOS mice exhibited complete estrous acyclicity. However, cyclicity was restored in PCOS mice consuming a C intake between 20-30kJ/day. Anovulation, as indicated by the presence of corpora lutea in the ovaries, was ameliorated at a C intake >20kJ/day. In contrast, dietary macronutrient composition had minimal effects on PCOS metabolic features. PCOS mice were more sensitive to C and F intake as they gained significantly more weight compared to controls at low C and F intakes of <25kJ/day each (P<0.05). This weight increase was correlated with a significant increase in adipocyte size in PCOS mice compared to controls (P<0.05). Furthermore, serum adiponectin levels were significantly decreased compared to controls at all macronutrient intakes (P<0.001) consistent with adipose tissue dysfunction in PCOS females. Moreover, PCOS mice were unable to regulate serum fasting glucose and cholesterol levels across varying macronutrient intakes, implying the hyperandrogenic PCOS environment impedes metabolic homeostasis in response to dietary changes (P<0.05). These findings provide evidence that PCOS traits can be ameliorated through dietary interventions, although hallmark reproductive and metabolic PCOS traits are differentially sensitive to dietary macronutrient balance.