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

4-vinylcyclohexene diepoxide (VCD), widely used in industry, is a hazardous compound that can cause premature ovarian 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 pregnant mice 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 ovarian reserve, while increasing microtia occurrences of F1 mice. The cytospread staining showed a significant inhibition of meiotic prophase I progression from the zygotene stage to the pachytene stage. Mechanistically, the expression level of DNA damage marker (γ-H2AX) and BAX/BCL2 ratios were significantly increased, and RAD51 and DMC1 were 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 intergenerational deleterious effects on the offspring. [Display omitted] •Maternal exposure to VCD causes intergenerational toxicity to offspring.•Maternal exposure to VCD leads to birth defects and sub-fertility in offspring.•Maternal exposure to VCD inhibits the progression of meiotic prophase I in fetal oocytes.•Maternal exposure to VCD during pregnancy reduces F1 oocyte number by causing meiosis arrest, DNA damage and apoptosis.