Bisphenol A exposure during pregnancy disrupts glucose homeostasis in mothers and adult male offspring.
Bisphenol A exposure during pregnancy disrupts glucose homeostasis in mothers and adult male offspring.
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DOI：
10.1289/ehp.1001993
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发表时间：
2010-09
影响因子：
10.4
通讯作者：
Nadal A
中科院分区：
文献类型：
--
作者：
Alonso-Magdalena P;Vieira E;Soriano S;Menes L;Burks D;Quesada I;Nadal A
双酚 A (BPA) 是一种广泛使用的内分泌干扰化学品，用作聚碳酸酯塑料制造中的基础化合物。在人类中，流行病学证据表明，成人接触 BPA 与患 2 型糖尿病和心脏病的风险较高有关。我们研究了环境相关剂量的 BPA 对怀孕期间小鼠葡萄糖代谢的作用，以及接触 BPA 对这些雌性小鼠以后生活的影响。我们还研究了子宫内接触 BPA 对后代代谢参数和胰腺功能的影响。怀孕小鼠在妊娠第 9-16 天期间接受媒介物或 BPA（10 或 100 μg/kg/天）治疗。对怀孕小鼠及其后代进行了葡萄糖代谢实验。与对照组相比，接触 BPA 会加剧妊娠期间产生的胰岛素抵抗，并与葡萄糖耐量下降以及血浆胰岛素、甘油三酯和瘦素浓度增加有关。与对照组相比，经 BPA 处理的怀孕小鼠的骨骼肌和肝脏中胰岛素刺激的 Akt 磷酸化有所减少。妊娠期间接触 BPA 对母亲产生长期影响：产后 4 个月，接受治疗的女性比未接受治疗的女性体重更重，血浆胰岛素、瘦素、甘油三酯和甘油水平更高，胰岛素抵抗也更大。与未接受治疗的母亲的后代相比，在 6 个月大时，子宫内暴露于该药物的雄性后代的葡萄糖耐量降低，胰岛素抵抗增加，并且血液参数发生改变。雄性后代的朗格汉斯胰岛呈现出改变的 Ca2+ 信号传导和胰岛素分泌。在雄性后代中，BrdU（溴脱氧尿苷）掺入胰岛素生成细胞的情况减少，但 β 细胞质量却没有变化。我们的研究结果表明，BPA 可能会导致与葡萄糖稳态相关的代谢紊乱，并且 BPA 可能是糖尿病的危险因素。
Bisphenol A (BPA) is a widespread endocrine-disrupting chemical used as the base compound in the manufacture of polycarbonate plastics. In humans, epidemiological evidence has associated BPA exposure in adults with higher risk of type 2 diabetes and heart disease. We examined the action of environmentally relevant doses of BPA on glucose metabolism in mice during pregnancy and the impact of BPA exposure on these females later in life. We also investigated the consequences of in utero exposure to BPA on metabolic parameters and pancreatic function in offspring. Pregnant mice were treated with either vehicle or BPA (10 or 100 μg/kg/day) during days 9–16 of gestation. Glucose metabolism experiments were performed on pregnant mice and their offspring. BPA exposure aggravated the insulin resistance produced during pregnancy and was associated with decreased glucose tolerance and increased plasma insulin, triglyceride, and leptin concentrations relative to controls. Insulin-stimulated Akt phosphorylation was reduced in skeletal muscle and liver of BPA-treated pregnant mice relative to controls. BPA exposure during gestation had long-term consequences for mothers: 4 months postpartum, treated females weighed more than untreated females and had higher plasma insulin, leptin, triglyceride, and glycerol levels and greater insulin resistance. At 6 months of age, male offspring exposed in utero had reduced glucose tolerance, increased insulin resistance, and altered blood parameters compared with offspring of untreated mothers. The islets of Langerhans from male offspring presented altered Ca2+ signaling and insulin secretion. BrdU (bromodeoxyuridine) incorporation into insulin-producing cells was reduced in the male progeny, yet β-cell mass was unchanged. Our findings suggest that BPA may contribute to metabolic disorders relevant to glucose homeostasis and that BPA may be a risk factor for diabetes.
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影响因子：
4.1
作者：
Rubin BS;Soto AM
通讯作者：
Soto AM
雌激素受体ERα调节胰腺胰岛素含量。
影响因子：
3.7
作者：
Alonso-Magdalena, Paloma;Ropero, Ana B.;Carrera, M. Pilar;Cederroth, Christopher R.;Baquie, Mathurin;Gauthier, Benoit R.;Nef, Serge;Stefani, Enrico;Nadal, Angel
通讯作者：
Nadal, Angel
在风险评估中，对鱼类生物标志物中内分泌干扰的筛查和测试是“路标”，而不是“交通信号灯”。
影响因子：
10.4
作者：
Hutchinson, Thomas H;Ankley, Gerald T;Segner, Helmut;Tyler, Charles R
通讯作者：
Tyler, Charles R
影响因子：
64.8
作者：
Kahn, Steven E.;Hull, Rebecca L.;Utzschneider, Kristina M.
通讯作者：
Utzschneider, Kristina M.
影响因子：
7.7
作者：
Jimenez-Chillaron, JC;Hernandez-Valencia, M;Patti, ME
通讯作者：
Patti, ME