Parental BPA exposure disrupts offspring transcriptomic profiles and impairs embryonic lineage specification during zygotic genome activation

Bisphenol A (BPA) is an endocrine-disrupting chemical known for its developmental toxicity. However, the impact of BPA on early embryonic development, particularly during zygotic genome activation (ZGA), remains underexplored. In this study, zebrafish embryos at 3.5 and 4.5 hours post-fertilization (hpf) were collected after 7-day parental exposure to 1.0 µM BPA for transcriptome sequencing. Transcriptomic data underwent differential gene expression functional enrichment and gene set enrichment analyses. Public single-cell transcriptome atlases of zebrafish embryos at different developmental stages (3.3, 4, and 4.8 hpf) were obtained to build signature matrices for digital cell type sorting of the bulk transcriptome using the CIBERSORTx algorithm. Results indicated that parental BPA exposure resulted in muted gene expression response, disturbed energy metabolism profile, and increased pro-inflammatory signatures during ZGA. Digital cell type deconvolution revealed altered cell composition, including deeper multilayer and enveloping layer cells and fewer margin cells. Furthermore, reductions in neural progenitor and heart primordium lineages, alongside expansions in primordial germ and mesendodermal lineages, potentially contribute to later-stage developmental abnormalities. This study elucidates the embryotoxic effects of BPA during the ZGA period, shedding light on the developmental perturbations from early-life exposure to this ubiquitous environmental contaminant.