Reproductive Developmental Biology Group, Reproduction and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC, United States.
Integrated Laboratory Systems, Inc., Research Triangle Park, NC, United States.
Reprod Toxicol. 2020 Aug;95:95-103. doi: 10.1016/j.reprotox.2020.05.006. Epub 2020 May 17.
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.
在子宫内接触亚砷酸盐（iAs）已知会增加生命后期的疾病风险。我们研究了在饮用水中暴露于 iAs 对雄性小鼠后代在产后和成年阶段的代谢和生殖参数的影响。从胚胎第 10-18 天（E）开始，怀孕的 CD-1 小鼠在饮用水中接触 iAs（作为亚砷酸钠），浓度分别为 0（对照）、10ppb（饮用水的 EPA 标准）和 42.5ppm（诱导小鼠肿瘤的剂量）。出生时，幼崽被寄养给未暴露的雌性。与对照组相比，在子宫内暴露于 10ppb 的雄性后代出生时体重增加。在子宫内暴露于 42.5ppm 的雄性后代体重增加趋势明显，且肛门生殖器距离更小。与对照组相比，iAs 暴露的幼崽体重在 3 周和 11 周时继续显著增加。在 5 个月大时，iAs 暴露的雄性表现出更高的体脂肪含量和葡萄糖不耐受。在子宫内暴露于 10ppb 的雄性后代循环中的瘦素水平高于对照组。此外，在子宫内暴露于 42.5ppm 的雄性后代出生的幼崽总数与对照组相比减少，并且在六个月的时间内平均每窝产仔数较低。这些结果表明，在子宫内暴露于人类相关浓度或诱导肿瘤浓度的 iAs 可能是成年雄性小鼠代谢和生殖功能障碍的发育起源的潜在原因。
