Regulation of Lipid Biology‐Associated Gene Expression in Granulosa Cells in Hyperandrogenic PCOS : A Possible Link Between Dyslipidemia and Hyperandrogenism

ABSTRACT Polycystic ovary syndrome (PCOS) is a heterogeneous reproductive endocrine condition in women, with implications in fertility and long‐term metabolic health. PCOS with hyperandrogen (HA‐PCOS; hyperandrogenic PCOS) has been recently identified as one of the four subtypes of PCOS. Dyslipidemia is known to be associated with clinical hyperandrogenism in PCOS. Indeed, patients with HA‐PCOS were found to have the highest incidence of dyslipidemia among patients with the other three subtypes of PCOS. In the present study, we identified genes involved in lipid‐associated processes (namely, lipid biosynthetic process, lipid catabolic process, hyperlipidemia, hypolipidemia and lipid homeostasis) whose expression are changed in granulosa cells from HA‐PCOS patients compared to those from non‐PCOS women, in order to identify molecular factors contributing to the highest risk of dyslipidemia incidence observed in patients with hyperandrogenic PCOS. We found 27 lipid biology‐associated genes (ACSM1, ACSM3, AGPAT4, AJUBA, ALDH1A2, CCDC3, LPL, P2RX1, PITPNM1, PRLR, PTGIS, SLC44A5, SPTSSB, ST8SIA5, IDH1, ITPKA, PPM1L, SPTLC2, ADRA2A, ASPG, IRS1, PLB1, IDH1, LCT, NUDT8, SMPDL3A and SYNE2) whose transcript levels are significantly downregulated or upregulated in granulosa cells of women with HA‐PCOS compared to those in control women. The majority of these genes have not been previously studied in the context of PCOS, and are possible candidates for further research to better understand the contribution of high androgen levels to dyslipidemia in PCOS. Targeting of high androgen‐induced dyslipidemia might be of high clinical importance in the treatment of women with HA‐PCOS.