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Arsenite exposure disturbs maternal-to-zygote transition by attenuating H3K27ac during mouse preimplantation
Longtao Yu1, Qiaoran Sun1, Ziying Huang2
1Institute of Stem Cell and Regenerative Biology, College of Animal Science and Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China; Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction (Huazhong Agricultural University), Ministry of Education, Wuhan, 430070, China.
Abstract:
Arsenite is commonly used as an insecticide, antiseptic and herbicide. It can enter the food chain via through soil contamination, and harm human health, including the reproductive systems. Early embryos, as the initial stage of mammalian life, are very sensitive to the environmental toxins and pollutants. However, whether and how arsenite disturbs the early embryo development remains unclear. Our study used mouse early embryos as a model and revealed that arsenite exposure did not cause reactive oxygen species production, DNA damage or apoptosis. However, arsenite exposure arrested embryonic development at the 2-cell stage by altering gene expression patterns. The transcriptional profile in the disrupted embryos showed abnormal maternal-to-zygote transition (MZT). More importantly, arsenite exposure attenuated H3K27ac modification enrichment at the promoter region of Brg1, a key gene for MZT, which inhibited its transcription, and further affected MZT and early embryonic development. In conclusion our study highlights arsenite exposure affects MZT by reducing the enrichment of H3K27ac on the embryonic genome, and ultimately induces early embryonic development arrest at the 2-cell stage.
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