Hydrogen sulfide donor sodium hydrosulfide modulates ovarian steroidogenesis and follicular integrity in a DHEA-induced rat model of polycystic ovary syndrome.

BACKGROUND

Hydrogen sulfide (H2S) has emerged as a potential regulator of ovarian physiology; however, its role in polycystic ovary syndrome (PCOS) remains incompletely understood. This study aimed to investigate the effects of the H2S donor sodium hydrosulfide (NaHS) on ovarian steroidogenesis, apoptosis and follicular remodelling in a dehydroepiandrosterone (DHEA)-induced rat model of PCOS.

METHODS

Thirty adult female Wistar rats were randomly assigned to control, vehicle, PCOS, NaHS, and PCOS+NaHS groups (n=6 each). PCOS was induced by daily subcutaneous injections (s.c) of DHEA (6 mg/100 g body weight) for 20 days. NaHS (200 μg/kg/day) was administered intraperitoneally (i.p.), either alone or in combination with DHEA. Serum hormone levels were analyzed, estrous cyclicity was tracked, and ovarian tissues were examined histologically for follicular development, apoptosis, and the expression of key steroidogenic enzymes (StAR, 3β-HSD, CYP19A1) and H2S-producing enzymes (CBS, CTH) at both protein and mRNA levels.

RESULTS

DHEA treatment resulted in disrupted estrous cyclicity, elevated serum estradiol and progesterone levels, reduced numbers of primordial, primary, Graafian follicles and corpora lutea, and increased cystic and atretic follicles. Apoptotic activity and the expression of StAR, 3β-HSD, and CYP19A1 were significantly elevated, whereas CBS and CTH expression levels were reduced. NaHS administration attenuated DHEA-induced alterations by improving estrous cyclicity, reducing follicular damage and apoptosis, downregulating steroidogenic enzyme overexpression, and partially restoring CBS and CTH expression.

CONCLUSIONS

Pharmacological supplementation with the H2S donor NaHS was associated with modulation of steroidogenic enzyme expression, apoptotic activity, and follicular architecture in a DHEA-induced PCOS model. These findings suggest a potential regulatory interaction between H2S-related pathways and ovarian dysfunction in PCOS, warranting further mechanistic investigation.