Transgenerational Reproductive Effects of Arsenite Are Associated with H3K4 Dimethylation and SPR‑5 Downregulation in Caenorhabditis elegans

Arsenic is a prevalent environmental toxin. Arsenic is associated with a wide variety of adverse effects; however, studies on whether As-induced toxicities can be transferred from parents to offspring have received little attention. Caenorhabditis elegans has become an important animal model in biomedical and environmental toxicology research. In this study, transgenerational reproductive toxicity by arsenite exposure and the underlying mechanisms in C. elegans were investigated over six generations (F0–F5). Following arsenite maternal exposure of the F0 generation, subsequent generations (F1–F5) were cultured under arsenite-free conditions. We found that the brood size of C. elegans was significantly reduced by arsenite exposure in F0 and that this reduction in brood size was also observed in the offspring generations (F1–F5), after the toxicant had been removed from the diet. In addition, adult worms from F0 and F1 generations accumulated arsenite and arsenate when F0 L4 larvae were exposed to arsenite for 24 h. We found that the mRNA level of H3K4me2 demethylase LSD/KDM1, spr-5, was significantly reduced in the F0 exposed generation and subsequent unexposed generations (F1–F3). Likewise, the mRNA levels of spr-5 were also significantly decreased in the F1–F3 generations. Moreover, dimethylation of global H3K4 was increased in the F0–F3 generations. Our study demonstrates that maternal arsenite exposure causes transgenerational reproductive effects in C. elegans, which might be associated with H3K4 dimethylation and SPR-5 downregulation.