Transcriptome profiling identified dysregulated signaling related to adipogenesis, metabolism, and inflammation in polycystic ovary syndrome patients

Polycystic ovary syndrome (PCOS) is a female endocrine disorder characterized by hyperandrogenism, chronic anovulation, and polycystic ovaries. PCOS is often accompanied by symptoms such as insulin resistance, abdominal obesity, and chronic inflammation. Adipose tissue is a crucial endocrine organ involved in metabolic disorders. Metabolic issues and chronic inflammation in PCOS are linked to dysfunctional adipose tissue. Mesenchymal progenitor cells (MPCs) are the precursor cells of adipocytes and can regulate the immune system. In this study, we used induced pluripotent stem cells (iPSCs) from patients with PCOS to derive MPCs and compare the transcriptome profiles between PCOS and HC iPSC-derived MPCs. We also challenged iPSC-derived MPCs with testosterone to assess the impact of androgen on MPCs. We found that 1026 genes differed between PCOS and HC iPSC-derived MPCs. Gene set enrichment analysis showed adipogenesis and metabolic function were reduced, but the inflammatory response was raised in PCOS iPSC-derived MPCs. The critical signals for early adipogenesis, including TGFβ, BMP, WNT, and CEBPA, differed between PCOS and HC iPSC-derived MPCs. After adipogenic induction, mature adipocytes were lower in PCOS iPSC-derived MPCs than HC. Lipolysis, the process involved in fat metabolism, was lower in adipocytes derived from PCOS MPCs than in HC. The testosterone treatment results indicated that genes related to oxidative phosphorylation and fatty acid metabolism were upregulated in HC iPSC-derived MPCs but downregulated in PCOS iPSC-derived MPCs. Short-term androgen stimulation may benefit body functions in HC. The impact of testosterone varied among individuals with HC and PCOS, possibly because of a genetic tendency towards PCOS. This study explains important factors that help us understand PCOS.