Maternal exposure to 4-vinylcyclohexene diepoxide during pregnancyinduces subfertility and birth defects of offspring in mice br

SSRN Electronic Journal(2023)

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摘要
4-vinylcyclohexene diepoxide (VCD), widely used in industry, is a hazardous compound that can cause prematureovarian failure, but whether maternal VCD exposure affects the health and reproduction of offspring is unknown.Here we focused on the effects of VCD on fertility and physical health of F1 and F2 offspring in mice. The pregnantmice were injected intraperitoneally with different dosages of VCD once every day from 6.5 to 18.5 days post-coitus(dpc). We showed that maternal exposure to VCD during pregnancy significantly reduced the litter size and ovarianreserve, while increasing microtia occurrences of F1 mice. The cytospread staining showed a significant inhibitionof meiotic prophase I progression from the zygotene stage to the pachytene stage. Mechanistically, the expressionlevel of DNA damage marker (gamma-H2AX) and BAX/BCL2 ratios were significantly increased, and RAD51 and DMC1were extensively recruited to DNA double strand breaks sites in the oocytes of offspring from VCD-exposed mothers.Overall, our results provide solid evidence showing that maternal exposure to VCD during pregnancy has intergener-ational deleterious effects on the offspring
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关键词
Intergenerational transmission,Fertility,Meiosis,Oocyte,Follicle
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