Carbon monoxide refines ovarian structure changes and attenuates oxidative stress via modulating of heme oxygenase system in a rat model of polycystic ovary syndrome: An experimental study.

Background: Carbon monoxide (CO), influences ovarian function, pregnancy, and placental health. Heme oxygenase (HO)-1 and its products, including CO, exhibit protective and anti-inflammatory properties.

Objective: This study investigates the protective effects of CO released by the carbon dioxide-releasing molecule (CORM)-2 against oxidative stress, functional and structural changes of the ovaries, and HO-1 expressions in female rats suffering from polycystic ovary syndrome (PCOS).

Materials and methods: In this experimental study, 24 Rattus norvegicus var. Albinus female rats (180-200 gr, 8 wk) were randomly divided into 4 groups (n = 6/each): control, CORM-2 (10 mg/kg), PCOS (induced by 4 mg/kg, intramuscular injection and a single dose of estradiol valerate), PCOS + CORM-2. Ovary histological changes were evaluated by crystal violet staining. Malondialdehyde (MDA) level and superoxide dismutase (SOD) activity of ovarian tissue were assessed using enzyme-linked immunosorbent assay. HO-1 expression was evaluated using Western blot.

Results: Corpus luteal formation significantly decreased in the PCOS group and was significantly restored with CORM-2 administration compared to the control group (p $<$ 0.05). The expression of ovarian HO-1 protein was reduced in the PCOS group compared to controls (p $<$ 0.01), and administration of CORM in PCOS rats significantly increased its expression (p $<$ 0.0001). In addition, CORM administration markedly reduced ovarian MDA levels and restored SOD activity (p $<$ 0.0001).

Conclusion: CORM-2 administration to PCOS rats created protective effects by reducing oxidative stress (reducing MDA level and restoring SOD activity) and increasing ovarian HO-1 protein.