LAUSR

Abstract Polycystic ovary syndrome (PCOS) is a complex, heterogeneous disorder characterized by reproductive, endocrine and metabolic abnormalities; however, its aetiology is unknown and current medical management relies solely on symptomatic treatment. Hyperandrogenism is a defining characteristic of PCOS, and diet is inherently associated since obesity is present in 40-80% of PCOS women. Dietary interventions are appealing as a powerful public health intervention to prevent or ameliorate the manifestation of PCOS, but the optimal diet for PCOS treatment remains unclear. Previously we proved in female mice that reproductive and metabolic traits contributing to the PCOS phenotype are strongly impacted by dietary macronutrient balance. Therefore, to determine the impact of dietary macronutrient balance on the development of PCOS, we provided our experimental mouse model of 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. All control mice cycled. Most PCOS mice exhibited complete estrous acyclicity, but despite the presence of hyperandrogenism, cyclicity was restored in PCOS mice consuming a C intake between 20-30kJ/day. Correspondingly, ovaries collected from PCOS mice with diet-restored cyclicity exhibited corpora lutea, confirming ovulations. As with cyclicity, ovulation dysfunction was ameliorated when PCOS mice consumed a C intake between 20-30kJ/day (P<0.05). Interestingly, PCOS mice that cycled were not the leanest PCOS females, displaying a higher average body weight (24.4g +/- 0.2) compared to controls (21.7g +/- 0.2; P<0.001). However, PCOS mice were able to maintain a body weight comparable to controls by reducing C intake to <20kJ/day (P<0.001). PCOS is associated with higher levels of circulating cholesterol, and regardless of diet, PCOS mice overall displayed a significant increase in cholesterol levels (61.5mg/dL +/- 2.7; P<0.05) compared to controls (53.1mg/dL +/- 2.2). This feature was aggravated by increasing F consumption (P<0.001), but decreased to control levels by reducing F intake to <20kJ/day (P<0.001). These findings provide evidence that PCOS traits can be ameliorated through dietary interventions to restore reproductive and metabolic abnormalities to control levels, although it appears that these hallmark PCOS traits are differentially sensitive to dietary macronutrient balance.