2-bromoacetamide impairs early embryonic development in mice in vitro accompanied by oxidative stress and mitochondrial alterations.
Abstract
Haloacetamides are nitrogen-containing disinfection byproducts formed during conventional water disinfection processes that are not currently regulated in drinking water standards. Their potential health risks have attracted increasing attention. Among them, 2-bromoacetamide (BAcAm) is particularly concerning due to its relatively high occurrence in disinfected water and potent toxicity. While BAcAm exposure has been reported to disrupt oocyte meiotic maturation in mice and humans, its effects on preimplantation embryonic development remain poorly understood. Here, we investigated the impact of BAcAm on mouse preimplantation embryonic development. Mouse preimplantation embryos were collected and cultured in vitro with different concentrations of BAcAm, and developmental progression was assessed. To characterize molecular changes associated with BAcAm exposure, 2-cell embryos were subjected to transcriptome sequencing, immunofluorescence and live-cell fluorescence assays. BAcAm exposure induced dose-dependent developmental arrest, predominantly at the 2-cell stage. Transcriptomic analysis revealed changes in the expression of genes related to the maternal-to-zygotic transition. BAcAm exposure was accompanied by altered mitochondrial features (increased ATP levels and a downward trend in mitochondrial membrane potential), elavated reactive oxygen species (ROS) levels and increased DNA damage. Supplementation with N-acetylcysteine attenuated both the developmental arrest and ROS elevation. BAcAm also altered histone modification profiles, with a significant decrease in me2H3K27 and downward trends in acH3K27 and me3H3K9. Collectively, BAcAm disrupted mouse preimplantation embryonic development and was associated with mitochondrial alterations, oxidative stress and altered histone modifications. These data revealed the toxic effects of BAcAm on early embryonic development and emphasized its potential adverse impacts on female reproductive health.