Upregulation of PD-L1 contributes to improving the apoptosis of granulosa cells via the PI3K/AKT pathway in PCOS.

Abstract

Polycystic ovary syndrome (PCOS) is a leading cause of anovulatory infertility and closely correlated with apoptosis in ovarian granulosa cells (GCs). Programmed cell death protein-1/programmed cell death ligand-1 (PD-1/PD-L1) pathway plays an important role throughout gestation and the pathogenesis of adverse pregnancy outcomes, but its mechanism in PCOS remains unclear. The RNA sequencing data for PCOS patients were downloaded from the Gene Expression Omnibus (GEO) databases. Bioinformatics analysis was conducted to identify differentially expressed PD-1/PD-L1 pathway genes (DEPPGs) and related signaling pathways. PCOS mouse model was established by injecting dehydroepiandrosterone (DHEA), apoptosis of ovarian GCs in PCOS mouse were detected by TUNEL staining. The main genes and proteins in the PI3K/AKT signaling pathway and apoptosis were detected by qRT-PCR and Western blot analyses after PD-L1 intervention in GCs. Finally, the hub gene of differentially expressed PI3K/AKT pathway genes (DEPAGs) in GCs was evaluated in PCOS patients. The DEPPGs in GCs and oocyte were identified, showing enrichment in Th1 and Th2 cell differentiation, apoptosis, and PI3K/AKT signaling pathway. More apoptosis was observed in ovarian GCs of PCOS mice. In vitro experiments showed that PI3K/AKT pathway was activated and the apoptosis of GCs was suppressed after PD-L1 intervention. The hub gene COL1A1 was upregulated in the GCs of PCOS patients. PD-L1 may reduce the apoptosis of GCs through PI3K/AKT signaling pathway activation, providing a novel strategy for inhibiting the apoptosis of GCs in PCOS.