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

In brief Aberrant lipid metabolism and dysregulated apoptosis in granulosa cells (GCs) may contribute to diminished ovarian reserve in patients with polycystic ovary syndrome (PCOS). This article elucidates the pivotal role played by S100A11. Abstract Apoptosis of ovarian GCs affects the development and maturation of oocyte in PCOS. The objective of our study was to examine the impact of S100A11 on GCs in individuals with polycystic ovary syndrome. We found that the S100A11 level was higher in the ovarian GCs 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 increasing oxidative stress 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 GC apoptosis and induced the lipid metabolism and oxidative stress to regulate the follicular reserve in PCOS. Our study provides a functional link between S100A11 expression and apoptosis and lipid metabolism in PCOS, providing new insights into disease mechanisms.