DBTCL exposure disrupts maternal-zygotic transition and mitochondrial function during early embryonic development.

Abstract

Dibutyltin dichloride (DBTCL) is a ubiquitous environmental contaminant. Prior research has established the reproductive toxicity, yet its precise impacts on embryonic developmental processes haven't been fully elucidated. The present study was designed to explore the influence of DBTCL exposure on early embryonic development in mice. This study demonstrated that exposure to DBTCL led to early embryonic developmental arrest. Through transcriptome sequencing, it was found that DBTCL exposure changed the overall gene expression profile in mouse 2-cell embryos. It suppressed the process of zygotic genome activation and the degradation of maternal mRNA, which consequently arrested the maternal-zygotic transition (MZT). Furthermore, mitochondrial function was also damaged under DBTCL treatment, as demonstrated by disordered mitochondrial distribution and a decline in mitochondrial membrane potential, and reduced ATP synthesis. Elevated levels of reactive oxygen species and superoxide anions in DBTCL-treated embryos suggested that DBTCL triggered oxidative stress. Moreover, embryos exposed to DBTCL exhibited significantly increased DNA damage. These changes were accompanied by reductions in the repressive histone marks H3K9me3, H3K27me2, and H3K27me3, which may be associated with the observed alterations in MZT. Collectively, these findings highlight the potential of DBTCL to inhibit early embryonic development, providing key experimental evidence for elucidating its developmental toxicity mechanisms.