College of Medicine, California Northstate University, Elk Grove, California.
Department of Animal Science, Michigan State University, East Lansing, Michigan.
J Appl Toxicol. 2019 Nov;39(11):1516-1531. doi: 10.1002/jat.3836. Epub 2019 Jul 23.
In both human and animals, in utero exposure to bisphenol A (BPA), an endocrine-disrupting chemical used in the production of plastics and epoxy resins, has been shown to affect offspring reproductive and metabolic health during adult life. We hypothesized that the effect of prenatal exposure to environmentally relevant doses of BPA will be evident during fetal organogenesis and fetal/postnatal growth trajectory. Pregnant ewes were administered BPA subcutaneously from 30 to 90 days of gestation (term 147 days). Fetal organ weight, anthropometric measures, maternal/fetal hormones and postnatal growth trajectory were measured in both sexes. Gestational BPA administration resulted in higher accumulation in male than female fetuses only at fetal day 65, with minimal impact on fetal/maternal steroid milieu in both sexes at both time points. BPA-treated male fetuses were heavier than BPA-treated female fetuses at fetal day 90 whereas this sex difference was not evident in the control group. At the organ level, liver weight was reduced in prenatal BPA-treated female fetuses, while heart and thyroid gland weights were increased in BPA-treated male fetuses relative to their sex-matched control groups. Prenatal BPA treatment also altered the postnatal growth trajectory in a sex-specific manner. Males grew slower during the early postnatal period and caught up later. Females, in contrast, demonstrated the opposite growth trend. Prenatal BPA-induced changes in fetal organ differentiation and early life growth strongly implicate translational relevance of in utero contributions to reproductive and metabolic defects previously reported in adult female offspring.
在人类和动物中，产前暴露于双酚 A（BPA），一种用于生产塑料和环氧树脂的内分泌干扰化学物质，已被证明会影响成年后代的生殖和代谢健康。我们假设，在胎儿器官发生和胎儿/产后生长轨迹期间，环境相关剂量的 BPA 产前暴露的影响将是明显的。从妊娠 30 天到 90 天（妊娠 147 天），给怀孕的母羊皮下注射 BPA。在两性中测量胎儿器官重量、人体测量指标、母体/胎儿激素和产后生长轨迹。妊娠 BPA 给药仅在胎儿第 65 天导致雄性胎儿的积累高于雌性胎儿，但在两性两个时间点对胎儿/母体类固醇环境的影响最小。与 BPA 处理的雌性胎儿相比，BPA 处理的雄性胎儿在胎儿第 90 天更重，但在对照组中没有这种性别差异。在器官水平上，产前 BPA 处理的雌性胎儿的肝脏重量减轻，而 BPA 处理的雄性胎儿的心脏和甲状腺重量增加，与它们的性别匹配的对照组相比。产前 BPA 处理还以性别特异性的方式改变了产后生长轨迹。雄性在早期产后期间生长较慢，后来赶上。相比之下，雌性表现出相反的生长趋势。产前 BPA 诱导的胎儿器官分化和早期生长变化强烈暗示了先前在成年雌性后代中报道的生殖和代谢缺陷的翻译相关性。
