In utero exposure to arsenite (iAs) is known to increase disease risks later in life. We investigated the effect of in utero exposure to iAs in the drinking water on metabolic and reproductive parameters in male mouse offspring at postnatal and adult stages. Pregnant CD-1 mice were exposed to iAs (as sodium arsenite) in the drinking water at 0 (control), 10 ppb (EPA standard for drinking water), and 42.5 ppm (tumor-inducing dose in mice) from embryonic day (E) 10–18. At birth, pups were fostered to unexposed females. Male offspring exposed to 10 ppb in utero exhibited increase in body weight at birth when compared to controls. Male offspring exposed to 42.5 ppm in utero showed a tendency for increased body weight and a smaller anogenital distance. The body weight in iAs-exposed pups continued to increase significantly compared to control at 3 weeks and 11 weeks of age. At 5 months of age, iAs-exposed males exhibited greater body fat content and glucose intolerance. Male offspring exposed to 10 ppb in utero had higher circulating levels of leptin compared to control. In addition, males exposed to 42.5 ppm in utero exhibited decreased total number of pups born compared to controls and lower average number of litters sired over a six-month period. These results indicate that in utero exposure to iAs at either human relevant concentration or tumor-inducing concentration is a potential cause of developmental origin of metabolic and reproductive dysfunction in adult male mice.

众所周知，在子宫内接触亚砷酸盐 (iAs) 会增加生命后期的疾病风险。我们研究了子宫内暴露于饮用水中的 iAs 对出生后和成年阶段雄性小鼠后代的代谢和生殖参数的影响。怀孕的 CD-1 小鼠从胚胎日（E ) 10–18。在出生时，幼崽被抚养给未暴露的雌性。与对照组相比，在子宫内暴露于 10 ppb 的雄性后代在出生时表现出体重增加。雄性后代在子宫内暴露于 42.5 ppm显示出体重增加和肛门生殖器距离更小的趋势。与对照组相比，在 3 周龄和 11 周龄时，暴露于 iAs 的幼崽的体重继续显着增加。在 5 个月大时，暴露于 iAs 的雄性表现出更高的体脂含量和葡萄糖耐受性。与对照相比，在子宫内暴露于 10 ppb 的雄性后代具有更高的瘦素循环水平。此外，与对照组相比，在子宫内暴露于 42.5 ppm 的雄性表现出出生的幼崽总数减少，并且在六个月的时间内平均产仔数也更低。这些结果表明，在子宫内 暴露于人类相关浓度或肿瘤诱导浓度的 iAs 是成年雄性小鼠代谢和生殖功能障碍发育起源的潜在原因。