Melatonin suppresses the seasonal estrus in female giant pandas.

In mammals, the pineal gland secretes melatonin, which serves as a crucial signal for interpreting photoperiod cues. As a seasonal breeder, the giant panda typically mates during the spring. To fully elucidate melatonin's influence on the seasonal estrus of female giant pandas, we conducted an in-depth analysis of urinary hormones. First, we found that urinary melatonin and gonadotropin-releasing hormone (GnRH) levels exhibit distinct seasonal variations over the annual cycle. From January to April, melatonin levels decline sharply from their annual peak, while GnRH levels rise rapidly and remain elevated throughout February, March, and April, precisely corresponding to the giant panda breeding season. Second, during female estrus, the estrogen metabolites peak occurs near the time when melatonin levels drop to their lowest values, and an inverse correlation between melatonin and estrogen metabolites persists both before and after the estrogen metabolites peak. Our analysis of urinary hormones revealed that melatonin exerts a significant suppressive effect on urinary GnRH and estrogen metabolites production prior to the onset of the seasonal estrus in giant pandas. Given the multipotent differentiation capacity of mesenchymal stem cells, we selected cultured giant panda umbilical cord mesenchymal stem cells (UC-MSCs) as an in vitro model for further study. Initially, we characterized the expression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in UC-MSCs following GnRH stimulation. Notably, these cells exhibited pituitary-like functional properties, including responsiveness to GnRH and expression of FSH and LH genes, making them suitable for modeling melatonin's effects. Subsequent experiments demonstrated that melatonin suppresses GnRH-induced LH and FSH mRNA expression in UC-MSCs in a dose-dependent manner and higher concentrations of melatonin were particularly effective. Collectively, our study not only elucidates the regulatory effects of melatonin on the seasonal estrous cycle of female giant pandas but also offers valuable new perspectives. These insights can potentially guide the development of conservation strategies for this endangered species, facilitating more targeted and effective efforts to safeguard its population.