Bisphenol A Exposure during Pregnancy Disrupts Glucose Homeostasis in Mothers and Adult Male Offspring

被引:365
作者
Alonso-Magdalena, Paloma [1 ,2 ]
Vieira, Elaine [1 ,2 ]
Soriano, Sergi [1 ,2 ]
Menes, Lorena [2 ,3 ]
Burks, Deborah [2 ,3 ]
Quesada, Ivan [1 ,2 ]
Nadal, Angel [1 ,2 ]
机构
[1] Univ Miguel Hernandez Elche, Inst Bioingn, Elche 03202, Spain
[2] Univ Miguel Hernandez Elche, Ctr Invest Biomed Red Diabet & Enfermedades Metab, Elche 03202, Spain
[3] Consejo Super Invest Cient, Inst Principe Felipe, Valencia, Spain
关键词
bisphenol A; diabetes; endocrine disruptors; estrogen; gestational diabetes; islet of Langerhans; pregnancy; xenoestrogens; INSULIN-RESISTANCE; ADIPOSE-TISSUE; CELL FUNCTION; BETA-CELLS; IN-VIVO; MECHANISMS; OBESITY; LEPTIN; ALPHA; PATHOGENESIS;
D O I
10.1289/ehp.1001993
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
BACKGROUND: 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. OBJECTIVE: 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. METHODS: Pregnant mice were treated with either vehicle or BPA (10 or 100 mu g/kg/day) during days 9-16 of gestation. Glucose metabolism experiments were performed on pregnant mice and their offspring. RESULTS: 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 post-partum, 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 beta-cell mass was unchanged. CONCLUSIONS: Our findings suggest that BPA may contribute to metabolic disorders relevant to glucose homeostasis and that BPA may be a risk factor for diabetes.
引用
收藏
页码:1243 / 1250
页数:8
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