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

Abstract

BackgroundBisphenol 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.ObjectiveWe 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.MethodsPregnant 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.ResultsBPA 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.ConclusionsOur findings suggest that BPA may contribute to metabolic disorders relevant to glucose homeostasis and that BPA may be a risk factor for diabetes.

Perinatal exposure to bisphenol A exacerbates nonalcoholic steatohepatitis-like phenotype in male rat offspring fed on a high-fat diet

“…Perinatal exposure to BPA altered early adipogenesis and increased the body weight of offspring (Rubin & Soto 2009, Somm et al 2009. A brief exposure to BPA during pregnancy has also been found to initiate insulin resistance in adult offspring (Alonso-Magdalena et al 2010). Consistent with these findings, results from our previous study have confirmed that perinatal exposure to BPA resulted in a higher body weight and body fat percentage, a greater mass of white adipocytes, hyperlipidemia, hyperleptinemia, and insulin intolerance in adult rat offspring (Wei et al 2011).…”

Long-term oral exposure to bisphenol A induces glucose intolerance and insulin resistance

“…Several studies in rodent models have reported that perinatal exposure to BPA increases the body weight of offspring at 6 months of age (Alonso-Magdalena et al 2010) and in adulthood (Somm et al 2009) as well as in the neonatal period (Howdeshell et al 1999, Rubin et al 2001, Rubin & Soto 2009). However, Ryan et al (2010) reported a contrary result that oral exposure to BPA during the perinatal period did not induce glucose intolerance later in life in CD-1 mice.…”

Bisphenol A in Chronic Kidney Disease

“…Progressive exposure to BPA can afect adiposity, glucose or insulin regulation, lipid proiles or other end-points relating to diabetes or metabolic syndrome [19][20][21][22][23][24][25][26][27].…”