Intrauterine exposure of mice to arsenite induces abnormal and transgenerational glycometabolism

The adverse, transgenerational effects on health caused by environmental pollutants are receiving increasing attention. For humans and mice, inorganic arsenic (iAs), a widespread environmental contaminant, is associated with diabetic phenotypes. However, the transgenerational effects of arsenite-induced changes in glucose metabolism in mice have not been fully investigated. In the present study, F0 pregnant mice were exposed to arsenite via drinking water (0, 0.5, 5, or 50 ppm NaAsO2) from gestational day 0 (GD0) until parturition. We examined the effects of arsenite exposure on the metabolic phenotypes and the levels of proteins and genes related to glucose metabolism of dams and their offspring (F1∼F4). Arsenite exposure altered the glucose tolerance of offspring. Notably, glucose transporter-2 (GLUT2) and insulin receptor substrate-1 (IRS1), which are related to the maintenance of glucose homeostasis, were also changed. The homeostasis assessment-insulin resistance (HOMA-IR), an indicator of insulin resistance, was higher in the offspring from the F0 female mice exposed to arsenite. Furthermore, imprinted genes, insulin-like growth factor 2 (IGF2) and potassium voltage-gated channel subfamily Q member 1 (KCNQ1), related to glycometabolism across multiple generations, were lower in the offspring. In sum, arsenite exposure during pregnancy transgenerationally affects glucose metabolism, which is related to altered levels of IGF2 and KCNQ1.