The objective of this study was to explore whether
hyperandrogenism induces epigenetic alterations of
peroxisome proliferator-activated receptor gamma 1 (PPARG1), nuclear
corepressor 1 (NCOR1), and
histone deacetylase 3 (HDAC3) genes in granulosa cells (GCs) of
polycystic ovary syndrome (PCOS) women and whether these alterations are involved in the ovarian dysfunction induced by
hyperandrogenism. Thirty-two infertile PCOS women and 147 infertile women with tubal blockage were recruited. PCOS women were divided into the
hyperandrogenism (HA) PCOS group (n = 13) and nonhyperandrogenism (N-HA) PCOS group (n = 19). Sixty female Sprague-Dawley rats were used for PCOS model establishment. In GCs of HA PCOS women, PPARG1
mRNA expression was lower, whereas NCOR1 and HDAC3
mRNA expression were higher than N-HA PCOS women and controls (P < 0.05). When all women were divided into successful and failed pregnancy subgroups according to the following clinical pregnancy outcome, we found lower PPARG1
mRNA levels and higher NCOR1 and HDAC3
mRNA levels in the failed subgroup of HA PCOS (P < 0.05). Two hypermethylated CpG sites in the PPARG1 promoter and five hypomethylated CpG sites in the NCOR1 promoter were observed only in HA PCOS women (P < 0.01 to P < 0.0005). The acetylation levels of
histone H3 at
lysine 9 and p21
mRNA expression were decreased in human GCs treated with
dihydrotestosterone in vitro (P < 0.05). PCOS rat models also showed alterations of PPARG1, NCOR1, and HDAC3
mRNA expression and methylation changes of PPARG1 and NCOR1, consistent with the results from humans.
Hyperandrogenism induces the epigenetic alterations of PPARG1, NCOR1, and HDAC3 in GCs, which are involved in the ovarian dysfunction of HA PCOS.