L-arginine supplementation attenuates ovarian oxidative stress in female rats subjected to chronic intermittent hypoxia.

Background: Systemic and organ-specific oxidative stress triggered by hypoxia is suggested to play a key role in germ cell apoptosis and DNA damage. This study was designed to investigate the impact of chronic intermittent hypoxia (CIH) on female fertility and evaluate the potential antioxidant effect of L-arginine (L-Arg) supplementation.

Methods: Adult female rats were allocated into three groups: controls (normoxic), hypoxic and hypoxic supplemented with L-Arg. After 12 weeks; hematocrit value was determined, body weight (BW) and ovarian weight were measured for the calculation of the gonado-somatic index. Plasma levels of luteinizing hormone (LH) and progesterone were estimated. Ovarian tissue malondialdehyde (MDA) and catalase were assessed, and caspase-3 enzyme expression was detected by immunohistochemistry.

Results: Compared to controls, CIH resulted in increased oxidative stress in the ovarian tissue, decreased ovarian weight, and increased frequency of irregular cycles and higher plasma level of LH in rats with either regular or irregular ovarian cycles. Histological examination of ovarian sections revealed areas of degeneration, atretic follicles, interstitial edema, congested vessels and inflammatory cell infiltration. Immunohistochemistry confirmed the presence of apoptosis by increased caspase-3 expression. Hypoxic rats pre-treated with L-Arg showed increased BW and ovarian weight, decreased ovarian tissue MDA and plasma LH accompanied by a lower incidence of irregular cycles and mortality. The histological picture was improved and caspase-3 expression was reduced.

Conclusion: Oxidative stress caused by CIH is detrimental to the structure and function of the corpus luteum with an increased risk of reduced fertility. L-Arg supplementation increases antioxidant capacity and improves hypoxia-induced fertility disorders.