Reproduction Abstracts

Women with Polycystic Ovary Syndrome are at increased risk of developing insulin resistance, obesity and dyslipidemia. Amplified metabolic perturbations during puberty may be a central factor contributing to metabolic phenotype of adult PCOS. Using a clinically realistic ovine model of PCOS we reported hyperinsulinaemia and early fatty liver changes, with no difference in body weight and adiposity, in adolescence.

Here we aimed to further examine metabolic events during transition from adolescence to adulthood. Pregnant Scottish Greyface ewes were treated biweekly with either 100 mg of testosterone propionate (TP) or vehicle control (C) from day 62–102 of gestation. Two cohorts of animals, adolescent 11 months old (C=5 TP=9) and adult 30 months old (C=11 TP=4), were investigated.

During puberty, but not fetal or early life, there was decreased adipogenesis in subcutaneous adipose tissue (SAT) accompanied by decreased circulating concentrations of fibroblast growth factor 21 (FGF21), leptin and adiponectin, and increased concentrations of fasting free fatty acids (FFA) (P<0.05) in prenatally androgenized sheep. This was countered by upregulated expression of FFA transporters in liver SLC27A2, SLC27A5, CAV2, FABP4 (P<0.05). As young adults, TP-exposed animals had increased body weight (P<0.05), increased insulin concentration (P<0.05) and FFA levels (P<0.05) but with no difference in FGF21, leptin and aidponectin levels. Histological analysis revealed that TP-exposed animals have decreased total number of adipocytes (P<0.05) and increased mean adipocyte size in SAT (P<0.05).

Altered adipogenesis in SAT of PCOS-like sheep and decreased levels of beneficial adipokines correlate with onset of puberty and hyperinsulinaemia and results in hypertrophy of adult SAT. This consequently lowers capacity of SAT to safely store fat and potentially explain metabolic perturbations observed in PCOS-like female sheep. These provide better understanding into the pathophysiology of PCOS from puberty to adulthood and give opportunities for early clinical intervention to ameliorate the metabolic phenotype of PCOS.