Departments of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA.
Departments of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
Reprod Toxicol. 2019 Apr;85:110-122. doi: 10.1016/j.reprotox.2019.03.002. Epub 2019 Mar 7.
Developmental exposure to endocrine disruptor bisphenol A (BPA) is associated with metabolic defects during adulthood. In sheep, prenatal BPA treatment causes insulin resistance (IR) and adipocyte hypertrophy in the female offspring. To determine if changes in insulin sensitivity mediators (increase in inflammation, oxidative stress, and lipotoxicity and/or decrease in adiponectin) and the intracrine steroidal milieu contributes to these metabolic perturbations, metabolic tissues collected from 21-month-old female offspring born to mothers treated with 0, 0.05, 0.5, or 5 mg/kg/day of BPA were studied. Findings showed prenatal BPA in non-monotonic manner (1) increased oxidative stress; (2) induced lipotoxicity in liver and muscle; and (3) increased aromatase and estrogen receptor expression in visceral adipose tissues. These changes are generally associated with the development of peripheral and tissue level IR and may explain the IR status and adipocyte hypertrophy observed in prenatal BPA-treated female sheep.
发育过程中接触内分泌干扰物双酚 A（BPA）会导致成年后出现代谢缺陷。在绵羊中，产前 BPA 处理会导致雌性后代出现胰岛素抵抗（IR）和脂肪细胞肥大。为了确定胰岛素敏感性介质的变化（炎症、氧化应激和脂肪毒性增加，以及脂联素减少）和细胞内甾体环境是否导致这些代谢紊乱，研究了来自接受 0、0.05、0.5 或 5mg/kg/天 BPA 处理的母亲所生的 21 月龄雌性后代的代谢组织。研究结果表明，产前 BPA 以非单调的方式（1）增加氧化应激；（2）在肝脏和肌肉中诱导脂肪毒性；（3）增加内脏脂肪组织中的芳香酶和雌激素受体表达。这些变化通常与外周和组织水平的 IR 发展有关，可能解释了在产前 BPA 处理的雌性绵羊中观察到的 IR 状态和脂肪细胞肥大。
