The importance of melatonin in ovaries of higher mammals

Melatonin is an endogenous mediator of photoperiod information and a molecular component of the circadian time-keeping system. In seasonal animals, melatonin synchronizes annual breeding via natural photoperiod signals. In humans, menstruation related psychopathologies have been linked to light and darkness and thereby, to melatonin. Melatonin acts on the ovary via the brain-hypothalamus-pituitary pathway and through its ovarian receptors. It is not only retained from the blood circulation, but also produced in the ovary; indeed levels of melatonin are higher in follicular fluid (correlated with follicular growth) than in serum. Melatonin regulates the expression of gonadotropin releasing hormone (GnRH) and receptor (GnRHR), which promotes the maintenance of corpus luteus in pregnancy, and the release of follicle stimulating hormone (FSH) and luteinzing hormone (LH), influencing their effect on follicular growth, ovulation, luteinization. Melatonin also alters steioroidogenesis in various mammals including humans, in a species-dependent manner. Additionally melatonin exerts antioxidant activity, protecting the ovulating oocyte from free radical damage and abolishing H2O2 inhibition on progesterone production. Accordingly it is apparently involved in various infertility conditions with oxidative stress, such as PCOS and endometriosis. Melatonin holds promise in the treatment of luteal phase defects and as a supplement to the in vitro maturation culture medium of germinal-vesicle-stage oocytes. Melatonin also holds promise in the preservation/restoration of fertility in cancer patients and may also protect ovarian follicles against radio/chemotherapy damage. Further clinical studies are needed to increase our understanding of the reproductive role of melatonin in higher mammals which may open new horizons for ovarian infertility management.