Beneficial effects of melatonin on mouse preimplantation embryo development and implantation potential: possible involvement of clathrin-mediated endocytosis.

In brief: Embryo implantation is a critical determinant of reproductive success, yet improving the implantation potential of in vitro-cultured embryos remains a major challenge in assisted reproductive technology. This study demonstrates that melatonin promotes mouse preimplantation embryo development and implantation potential and provides evidence that CME-related processes may contribute to these beneficial effects. Abstract: Melatonin is a pleiotropic hormone with essential roles in mammalian reproduction. Our previous study demonstrated that melatonin promotes human oocyte maturation and early embryo development through enhancement of clathrin-mediated endocytosis (CME). In the present study, we investigated whether a similar melatonin-associated regulatory relationship is also observed during mouse preimplantation embryo development and implantation. Following concentration optimization, mouse zygotes were cultured with 10-9 M melatonin, 20 μM dynasore (a pharmacological inhibitor of dynamin-dependent endocytosis), or their combination. Melatonin supplementation significantly increased blastocyst formation and subsequent implantation potential. Conversely, dynasore treatment reduced blastocyst developmental progression and markedly impaired implantation potential. Importantly, melatonin supplementation significantly improved the implantation potential of dynasore-treated embryos. These findings demonstrate that melatonin promotes mouse preimplantation embryo development and implantation potential, and suggest that CME-related processes may contribute to these beneficial effects. Together with our previous findings in human oocytes and early embryos, the present study provides evidence supporting a shared melatonin-associated regulatory relationship between human and mouse reproductive systems. Given that suboptimal embryo implantation remains a major limitation in assisted reproductive technology, our findings suggest that melatonin supplementation warrants further investigation as a potential strategy for optimizing in-vitro embryo culture conditions and improving implantation outcomes.