Advanced glycation end products promote polycystic ovary syndrome by regulating AMH via PI3K/Akt/SF1 signaling pathway

Abstract

Abstract Background：Advanced glycation end products (AGEs) are involved in the pathogenesis of polycystic ovary syndrome (PCOS)and high concentrations of anti-Müllerian hormone (AMH) are considered one of the primary causes of anovulation in women with PCOS. However, the specific mechanism of action remains unclear. Method and Results: Ovarian granulosa cells (KGN cells) were treated with AGEs at different concentrations and times. The results showed that pretreatment with AGEs concentration-dependent and time-dependent affected the expression of AMH and SF1. PCNA expression was suppressed by AGEs treatment, and the ratio of the apoptosis-related protein Bax/Bcl2 was elevated. Tetrazolium colorimetric assay shows the same results. Granulosa cells caused by AGE to induce apoptosis could be significantly reversed in KGN cells transfected with AMH siRNA. AMH and the Bax/Bcl2 ratio expression were reduced after SF1 expression was inhibited. Inhibition of the PI3K upregulated PCNA, SF1 and AMH expression. Additionally, in ovarian tissues of AGEs group and PCOS group, the expression of AMH and SF1 increased, accompanied with marked up-regulation of the phosphorylation of PI3K and Akt expression. And the ratio of Bax/Bcl2 increased, while the expression of PCNA was opposite. Conclusions: AGEs increase the level of AMH (Anti-Mullerian Hormone) in ovarian granulosa cells, promoting apoptosis and restricting cell proliferation, thus leading to PCOS in rats. Studies suggest that SF1 may be a crucial target for AGE-mediated AMH production, involving the phosphorylation of the PI3K/Akt signaling pathway.