BHPF inhibits early embryonic development in mice by disrupting maternal-to-zygotic transition and mitochondrial...

Fluorene-9-bisphenol (BHPF), a prevalent substitute for bisphenol A (BPA), has become a widespread endocrine disruptor found in numerous consumer products. Despite extensive research on its toxicological profile, the specific effects of BHPF on reproduction, particularly during early embryonic development, remain unclear. Therefore, in our study, we used an in vitro culture system of mouse embryos to treat fertilized eggs with different concentrations of BHPF, and applied immunofluorescence, cell live staining and transcriptome sequencing to explore the effects of BHPF on early embryonic development and related mechanisms. Our study demonstrates that BHPF exposure causes significant developmental arrest in early embryonic stages. Transcriptomic analysis revealed that BHPF exposure altered gene expression at the 2-cell stage, notably impairing zygotic genome activation and maternal mRNA degradation, which disrupted the maternal-to-zygotic transition. Furthermore, BHPF exposure impaired mitochondrial function, as illustrated by altered mitochondrial distribution, reduced membrane potential, and decreased ATP production. Oxidative stress and DNA damage in 2-cell embryos were linked to the accumulation of reactive oxygen species and superoxide anions induced by BHPF. Additionally, BHPF-treated embryos exhibited altered histone modification patterns, suggesting epigenetic disruptions. Overall, these results indicate that BHPF has the potential to disrupt early embryonic development, raising concerns regarding its safety as a BPA substitute.