Association of ovarian inflammation and hormonal dysregulation: a candidate mechanism underlying polycystic ovary syndrome

Abstract

Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by female infertility, menstrual irregularities, and hormonal imbalance, leading to impaired reproductive health. Hyperandrogenemia is considered a central endocrine feature and a key contributor to PCOS pathophysiology. A dehydroepiandrosterone (DHEA)-induced mouse model was established to investigate transcriptomic alterations in granulosa cells (GCs) and their association with endocrine and inflammatory changes in PCOS. Model validation was performed using histological analysis (H&E staining), estrous cycle analysis, Western blotting of estrogen receptors (ERα and ERβ), and serum hormone profiling by ELISA. The PCOS model exhibited typical phenotypes, including polycystic ovarian morphology, estrous cycle arrest, and elevated testosterone (T), luteinizing hormone (LH), and LH/FSH ratios. Increased ERα expression was observed in ovarian GCs. RNA sequencing (RNA-seq) identified 161 differentially expressed genes, enriched in TNF signaling, NF-κB signaling, and steroid hormone biosynthesis pathways. In vitro, T-treated primary GCs showed increased ERα/ERβ ratio and enhanced pro-inflammatory signaling, with suppression of anti-inflammatory markers, consistent with in vivo findings. Overall, these findings support an association between endocrine alterations and inflammatory responses in ovarian GCs during PCOS. In conclusion, inflammatory factor expression in GCs was significantly associated with reproductive hormone dysregulation in PCOS, suggesting a potential hormone–inflammation interaction axis in the pathophysiology of PCOS.