Meteorin-like protein (metrnl) mediates exercise-related reproductive disorders in female rats

Exercise provides significant benefits for most women, but adverse effects on reproduction can and do occur. Increased frequency, duration, and intensity of exercise are associated with a higher risk of female infertility. In particular, exercise-induced reproductive dysfunction is linked to alterations in the hypothalamic-pituitary-gonadal (HPG) axis. However, the role of meteorin-like protein (metrnl), as an exercise-induced myokine, in female reproductive function and HPG axis is not yet fully understood. In this study, we investigated the effects of metrnl, compared with moderate-intensity exercise, on reproductive behavior and the HPG axis in female rats. Female rats with regular estrous cycles were randomly allocated into three groups (n = 9 per group), and subjected to deionized water (1 mL/kg), metrnl (1 µg/day) or moderate-intensity exercise (swimming: 30 minutes/day, 5 days/week) for about 19 consecutive days. The results showed that metrnl administration reduced the time spent near the male rat and the male preference ratio, indicators of sexual motivation. It also decreased hypothalamic GnRH expression (in the median eminence and preoptic area), serum concentrations of reproductive hormones (follicle-stimulating hormone and anti-Müllerian hormone), and the numbers of ovarian follicles (primordial and primary follicles), similar to the effects of moderate-intensity exercise. Furthermore, metrnl concentrations in serum remained unchanged in female rats treated with metrnl and exercise. In conclusion, metrnl treatment reduced sexual incentive motivation and impaired normal HPG axis function in female rats. These findings suggest that exercise-induced metrnl may be a pivotal exerkine associated with decreased sexual function and HPG axis impairment due to exercise in women.