Altered m A modification is involved in up-regulated expression of FOXO3 in luteinized granulosa cells of non-obese polycystic ovary syndrome patients.

The pathophysiology of polycystic ovary syndrome (PCOS) is characterized by granulosa cell (GC) dysfunction. m A modification affects GC function in patients with premature ovarian insufficiency (POI), but the role of m A modification in PCOS is unknown. The purpose of the prospective comparative study was to analyse the m A profile of the luteinized GCs from normovulatory women and non-obese PCOS patients following controlled ovarian hyperstimulation. RNA m A methylation levels were measured by m A quantification assay in the luteinized GCs of the controls and PCOS patients. Then, m A profiles were analysed by methylated RNA immunoprecipitation sequencing (MeRIP-seq). We reported that the m A level was increased in the luteinized GCs of PCOS patients. Comparative analysis revealed differences between the m A profiles from the luteinized GC of the controls and PCOS patients. We identified FOXO3 mRNA with reduced m A modification in the luteinized GCs of PCOS patients. Selectively knocking down m 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 A-mediated transcription of FOXO3 in the luteinized GCs of PCOS patients. Furthermore, we demonstrated that the involvement of m 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 A modification was involved in up-regulated expression of FOXO3 mRNA in the luteinized GCs from non-obese PCOS patients following controlled ovarian hyperstimulation.