Melatonin alleviates UV-induced embryonic toxicity via PARP1 expression in early mouse embryos.

Maintaining genome integrity is essential for preimplantation embryos, yet light poses a significant genotoxic threat. The application of assisted reproductive technologies (ART) increases embryo exposure to environmental factors, with ultraviolet (UV) light being particularly concerning. UV can cause various forms of DNA damage, such as sister chromatid exchange and DNA breakage in preimplantation embryos. Melatonin (MLT), a neuroendocrine hormone secreted by the pineal gland, positively influences various physiological processes, including regulating DNA damage responses. Here, we demonstrated that short-term UV exposure significantly impairs in vitro embryo development. UV exposure markedly disrupted the expression of Poly (ADP-ribose) polymerase 1 (Parp1) and DNA-damage-response genes involved in two major DNA repair pathways homologous recombination (HR) and non-homologous end-joining (NHEJ). However, the MLT supplement effectively rescued UV-induced developmental hindrance. Further investigations revealed that MLT could restore Parp1 expression, reduce oxidative stress, apoptosis, mitochondrial dysfunction, and even DNA damage in embryos exposed to UV. Importantly, MLT markedly alleviated the developmental impairment induced by PARP1 inhibition in normal embryos, underscoring the crucial role of PARP1 in MLT-mediated DNA repair. Moreover, RS-1, an agonist of the key HR protein RAD51, protected against UV-induced DNA damage in early mouse embryos comparable to MLT treatment. Overall, these findings reveal that short-term UV exposure adversely affects early embryo cleavage and development while highlighting the protective role of MLT against such damage.