Leptin mediates the effects of melatonin on female reproduction in mammals.

Melatonin is a natural molecule produced in the pineal gland and other tissues. It participates in numerous biological activities including the regulation of reproduction. However, the mechanism by which melatonin affects mammalian female reproductive performance is not fully investigated. In the present study, it was observed that melatonin positively regulated the level of leptin in female mouse and pig. To understand the potential association between melatonin and leptin on the female reproductive activities, the melatonin receptor 1 MT1 knockout (MT1-/- ) mouse and Leptin knockout (Leptin-/- ) pig were created. It was found that the deficiency of M T1 caused low leptin secretion and litter size in mouse. Meanwhile, the deletion of leptin in pig did not affect melatonin production, but significantly reduced follicle-stimulating hormone, estradiol-17β (E2), and Luteinizing hormone and increased progesterone (P) at estrum stage, which also led to smaller litter size than that in control. Melatonin treatment increased the production of leptin in pigs, while the supplementary of leptin was also able to improve the ovulation number, polar body rates, and expression of StAR in MT1-/- females. Therefore, it is first time, we described that leptin is the downstream target of melatonin in regulating female reproduction. These findings provide the novel information on the physiology of melatonin in animal reproduction.