Overexpression of renin-angiotensin system peptides and receptors (OVRAS) in androgen-induced PCOS mouse ovaries.

Abstract

PURPOSE: The ovarian renin-angiotensin system (OVRAS) plays a key role in ovarian physiology and pathology, regulating angiogenesis, steroidogenesis, follicular development, and ovulation. This study examines OVRAS expression in normal and dihydrotestosterone (DHT)-induced polycystic ovary syndrome (PCOS) mouse model to elucidate its role in PCOS pathogenesis. METHODS: Ovarian tissues from normal and DHT-treated mice were analyzed by double and triple immunofluorescence to localize angiotensin peptides (Ang II/III, Ang 1-7) and their receptors (AT1R, AT2R, MasR) within granulosa (GCs), theca (TCs), follicular contents, and interstitial cells (ICs) at preantral and antral stages. RESULTS: Normal ovaries exhibited stage-specific OVRAS expression, with Ang 1-7 progressively localizing toward the oocyte in antral follicles and Ang II-III showing strong expression in cells adjacent to the antrum. In DHT-treated ovaries, OVRAS was dysregulated, showing irregular Ang 1-7 staining in GCs, decreased AT1R, increased AT2R, and loss of Mas1R expression. DHT-PCOS follicles displayed impaired development, thickened theca layers, and OVRAS overexpression in ICs. The zona pellucida (ZP) was strongly stained in normal follicles but weakened in the distorted ZPs of DHT-treated mice. CONCLUSIONS: OVRAS shows hormone-regulated expression during normal folliculogenesis and is disrupted in the DHT-induced PCOS mouse model, paralleling human pathology. Its upregulation in interstitial cells following androgen exposure is associated with theca cell hyperplasia and excess androgen production, suggesting a role in PCOS-related follicular dysfunction. These results position OVRAS as a potential molecular marker and therapeutic target in ovarian disorders. Further studies are needed to clarify its function in follicular maturation and oocyte quality. .