Endocrine Abstracts

JOINT2368

There are three main functional fat depots in the body: subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and bone marrow adipose tissue (BMAT). In women with PCOS the SAT is dysfunctional with larger adipocytes and increased inflammation. This is recapitulated in the clinically realistic ovine model of PCOS using prenatal androgenisation. As BMAT is difficult to access and has not been studied in PCOS we aimed to use PCOS-like sheep to investigate the structure and function of BMAT. Pregnant Scottish Greyface sheep were treated with testosterone propionate (100 mg) or vehicle control twice weekly from day 62 to day 102 of a 147-day pregnancy. The female offspring exposed to increased prenatal androgens in utero develop the features of PCOS. BMAT was collected from adult offspring at 30 months of age (PCOS-like sheep n = 4; Control n = 6) and fixed for histological analysis and frozen for assessment of gene expression. The number of adipocytes per 3 mm³ (P = 0.78) and size of the adipocytes (P = 0.31) in BMAT was no different in PCOS-like sheep when compared to contemporaneous controls. PCOS-like sheep had increased expression of the inflammatory markers TNF (P = 0.0128), IL6 (P = 0.0013) and the macrophage marker CD68 (P = 0.0206) in BMAT. We therefore performed an additional unbiased analysis of BMAT gene expression in PCOS-like sheep using RNAseq. There was differential expression of 604 genes when compared to controls (232 down and 373 up) in PCOS-like sheep BMAT. Ingenuity Pathway Analysis highlighted up-regulation of inflammatory pathways with significant increases in activation, recruitment and degranulation of leukocytes, synthesis and metabolism of reactive oxygen species, recruitment and migration of phagocytes and the immunogenic cell death signalling pathway. Interestingly the top two canonical pathways altered were related to bone health linked to osteoclast and chondrocyte function suggesting increased bone resorption and remodelling. These results suggest that in PCOS immune cells may be developing in a more inflammatory environment and they already show functional alterations. Additionally, there may be a local effect on bone health. This suggests a possible mechanistic link to the systemic adverse inflammatory environment in PCOS.