Altered m<sup>6</sup>A modification is involved in up‐regulated expression of <i>FOXO3</i> in luteinized granulosa cells of non‐obese polycystic ovary syndrome patients
Shen Zhang, Wen-Li Deng, Qiongyou Liu, Pei‐Yu Wang, Wei Yang, Wuhua Ni
Abstract
Abstract The pathophysiology of polycystic ovary syndrome (PCOS) is characterized by granulosa cell (GC) dysfunction. m 6 A modification affects GC function in patients with premature ovarian insufficiency (POI), but the role of m 6 A modification in PCOS is unknown. The purpose of the prospective comparative study was to analyse the m 6 A profile of the luteinized GCs from normovulatory women and non‐obese PCOS patients following controlled ovarian hyperstimulation. RNA m 6 A methylation levels were measured by m 6 A quantification assay in the luteinized GCs of the controls and PCOS patients. Then, m 6 A profiles were analysed by methylated RNA immunoprecipitation sequencing (MeRIP‐seq). We reported that the m 6 A level was increased in the luteinized GCs of PCOS patients. Comparative analysis revealed differences between the m 6 A profiles from the luteinized GC of the controls and PCOS patients. We identified FOXO3 mRNA with reduced m 6 A modification in the luteinized GCs of PCOS patients. Selectively knocking down m 6 A methyltransferases or demethylases altered expression of FOXO3 in the luteinized GCs from the controls, but did not in PCOS patients. These suggested an absence of m 6 A‐mediated transcription of FOXO3 in the luteinized GCs of PCOS patients. Furthermore, we demonstrated that the involvement of m 6 A in the stability of the FOXO3 mRNA that is regulated via a putative methylation site in the 3’‐UTR only in the luteinized GCs of the controls. In summary, our findings showed that altered m 6 A modification was involved in up‐regulated expression of FOXO3 mRNA in the luteinized GCs from non‐obese PCOS patients following controlled ovarian hyperstimulation.