Endocrine Abstracts

JOINT2335

Prenatally androgenised female sheep are a clinically realistic model of PCOS. In adolescence (11 months of age) there is reduced subcutaneous adipogenesis and in adulthood (30 months of age) there is increased subcutaneous adipose tissue (SAT) dysfunction with inflammation. We hypothesised that analysis of adipose tissue in young adults (20 months of age), after adipogenesis is complete but before inflammation is manifest, would give insights into the evolution of adipose tissue dysfunction in PCOS. Pregnant Scottish Greyface sheep were treated intramuscularly with testosterone propionate (100 mg) or vehicle control twice weekly from day 62-102 of gestation (147 days) and their female offspring were studied. Two cohorts of weight-matched PCOS-like sheep and contemporaneous controls were investigated. At 20 months of age the SAT of young adult PCOS-like sheep (n = 10) and control sheep (n = 10) was examined by RNAseq and fixed for histochemical analysis. At 30 months of age PCOS-like sheep SAT (n = 4) and control sheep SAT (n = 4) underwent histochemical analysis. In addition, SAT was collected from obese adult women with PCOS (n = 12) and obese adult women without PCOS (n = 12) for histochemical analysis. RNAseq analysis of young adult PCOS-like sheep SAT showed that a total of 792 genes were differentially expressed when compared to control sheep (406 upregulated; 386 downregulated). Ingenuity pathways analysis highlighted upregulation of fibrosis signalling pathways, extracellular organisation pathways and the assembly of collagen fibrils in the SAT of PCOS-like sheep. RT-PCR confirmed that POSTN, which is associated with tissue remodelling and fibrosis, was increased (P < 0.05) in PCOS-like sheep SAT as were COL1A1 (P < 0.05), COL1A2 (P < 0.05) and COL3A1 (P < 0.01). Masson’s Trichrome stain showed an increased area of fibrosis in SAT of PCOS-like sheep (P < 0.05) when compared to controls. This increased fibrosis was also seen in both adult PCOS-like sheep (P < 0.05) and obese women with PCOS (P < 0.05) when compared to controls. Early fibrotic changes in SAT occurs in young adult PCOS-sheep and this change is also seen in adulthood and in adult women with PCOS. In young adult PCOS-like sheep SAT fibrosis is present before SAT inflammation is detected. SAT fibrosis might provide a barrier to healthy adipocyte expansion and have a mechanistic role in the development of the detrimental inflammatory environment in PCOS.