Host: The Japanese Society of Toxicology
Name : The 51st Annual Meeting of the Japanese Society of Toxicology
Date : July 03, 2024 - July 05, 2024
Although the molecular mechanisms of intergenerational transmission of effects by environmental factors are still largely unclear, the sperm epigenome will be involved in the transmission of effects mediated through sperm.
We are studying the mechanisms of the effects of arsenic, an environmental chemical, on the next generation. We found that gestational arsenic exposure of C3H mice, whose males are prone to developing liver tumors after growth, increases liver tumors in the F2 through their F1 males. We also found that gestational arsenic exposure induces genome-wide DNA hypomethylation in F1 sperm, and that the number of hypomethylated CpG are increased, especially in the LINE and LTR. Since hypomethylation of retrotransposons leads to adverse transposition activity and has been reported to be involved in carcinogenesis in somatic cells, it may contribute in part to the mechanism of liver tumor increase in arsenic F2 groups. Furthermore, the methylation state of arsenic F1 sperm was maintained in arsenic F2 embryos, whereas that was cancelled in arsenic F2 sperm. Our experimental system of gestational arsenic exposure in C3H mice has shown no increase in liver tumors in the F3, and the results of F2 sperm support the above discussion.
Recently, we have shown that genome-wide DNA hypomethylation occurs in type A spermatogonia of arsenic F1, but there is no increase in hypomethylated CpG in LINE. Arsenic may affect the expression of Dnmt and Tet during spermatogenesis after type A spermatogonia and induce an increase in hypomethylated CpG in F1 sperm.
