S100A11 promotes lipid metabolism and activates the apoptosis in polycystic ovary syndrome

Apoptosis of ovarian granulosa cells (GCs) affects the development and maturation of oocyte in Polycystic ovary syndrome (PCOS).The objective of our study was to examine the impact of S100A11 on granulosa cells in individuals with polycystic ovary syndrome. We found that the S100A11 level was higher in the ovarian granulosa cells of PCOS patients and ovarian tissue of PCOS mouse models. S100A11 overexpression experiments demonstrated a decrease in the cell proliferation, upregulating the apoptosis and blocking the cell cycle. Immunofluorescence staining showed that S100A11 proteins were mainly located in the nucleus. Integrating the RNA-seq and ChIP-seq, this study found that S100A11 mainly regulated the genetic transcription and lipid metabolism. Furthermore, lipid accumulation and oxidative stress increasing were detected in the S100A11 overexpression group. We also revealed that S100A11 upregulated the p-DRP1 Ser616 to induce the mitochondrial fission.In conclusion, S100A11 upregulated the phospho-DRP1 to activate ovarian granulosa cell apoptosis and induced the lipid metabolism and oxidative stress to regulate the follicular reserve in PCOS. The findings present a novel therapeutic concept for polycystic ovary syndrome.