Genome-wide identification and single-cell transcriptomic analysis of the mcm gene family in zebrafish reveals its role in TCDD-induced reproductive toxicity.

In recent years, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a typical persistent organic pollutant, has posed a serious threat to aquatic organisms and human reproductive health. However, the molecular mechanism by which it induces reproductive toxicity through interference with DNA replication remains unclear. In this study, we systematically analyzed the mcm gene family members in zebrafish through genome-wide identification. Combined with single-cell transcriptomic data (GSE193758) and molecular docking simulations, we investigated the impact of TCDD on mcm expression in testicular tissue and the interaction mechanism. A total of nine mcm genes were identified. Phylogenetic analysis revealed high conservation with other vertebrates. The single-cell expression atlas revealed that mcm genes are highly expressed in spermatogonia and early spermatocytes but downregulated in terminally differentiated cells. TCDD treatment led to significant upregulation of mcm2-7 in Leydig cells and selectively affected the mcm expression patterns across different cell types. Molecular docking simulations predicted potential binding interactions between TCDD and Mcm2-7 proteins (binding energy < -5.0 kcal/mol).This study is the first to reveal the potential role of the mcm gene family in TCDD-induced reproductive toxicity in zebrafish, providing a new perspective for understanding its environmental risk and toxicity mechanisms.