Sex-specific transgenerational effects of preconception exposure to arsenite: metabolic phenotypes of C57BL/6 offspring.

Chronic exposure to inorganic arsenic (iAs) has been linked to diabetes in both humans and mice, but the role of iAs exposure prior to conception and its transgenerational effects are understudied. The present study investigated transgenerational effects of preconception iAs exposure in C57BL/6J mice, focusing on metabolic phenotypes of G1 and G2 offspring. Body composition and diabetes indicators, including fasting blood glucose, fasting plasma insulin, glucose tolerance, and indicators of insulin resistance and beta cell function, were examined in both generations. The results suggest that the preconception iAs exposure in the parental (G0) generation induced diabetic phenotypes in G1 and G2 offspring in a sex-dependent manner. G1 females from iAs-exposed parents developed insulin resistance while no significant effects were found in G1 males. In the G2 generation, insulin resistance was observed only in males from iAs-exposed grandparents and was associated with higher bodyweights and adiposity. Similar trends were observed in G2 females from iAs-exposed grandparents, but these did not reach statistical significance. Thus, preconception iAs exposure altered metabolic phenotype across two generations of mouse offspring. Future research will investigate the molecular mechanisms underlying these transgenerational effects, including epigenomic and transcriptomic profiles of germ cells and tissues from G0, G1 and G2 generations.