The molecular mechanism underlying melatonin-mediated repair of ovarian damage in mice exposed to abnormal light cycles.

This study aimed to investigate the molecular mechanisms by which melatonin (MLT) mitigates ovarian damage in mice exposed to abnormal light cycles. Female C57BL/6 mice from the same batch were randomly assigned to five experimental groups: normal light cycle (LD), reversed light cycle (DL), reversed light cycle with MLT supplementation (MDL), constant light (LL), and constant light with MLT supplementation (MLL). Models of reversed and constant light exposure were established, and exogenous MLT was administered. The results indicated that MLT significantly alleviated ovarian developmental impairment induced by abnormal light cycles, reduced oocyte apoptosis, and attenuated the downregulation of Ddx4, androgen receptor (Ar), and estrogen receptor alpha (Erα) protein expression levels. RNA-seq analysis identified key genes involved in ovarian development, including Insl3, Runx2, and Timp1. Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that differentially expressed genes were significantly enriched in biological processes related to steroid biosynthesis, ovarian follicle development, female gonad development, regulation of reproductive processes, apoptosis regulation, circadian rhythm, and associated signaling pathways. These findings suggest that MLT regulates ovarian germ cell development and estrogen synthesis signaling pathways through modulation of Ddx4, Ar, and Erα expression.