Transgenerational effects of maternal bisphenol: a exposure on offspring metabolic health

J Dev Orig Health Dis. 2019 Apr;10(2):164-175. doi: 10.1017/S2040174418000764. Epub 2018 Oct 26.

Abstract

Exposure to the endocrine disruptor bisphenol A (BPA) is ubiquitous and associated with health abnormalities that persist in subsequent generations. However, transgenerational effects of BPA on metabolic health are not widely studied. In a maternal C57BL/6J mice (F0) exposure model using BPA doses that are relevant to human exposure levels (10 μg/kg/day, LowerB; 10 mg/kg/day, UpperB), we showed male- and dose-specific effects on pancreatic islets of the first (F1) and second generation (F2) offspring relative to controls (7% corn oil diet; control). In this study, we determined the transgenerational effects (F3) of BPA on metabolic health and pancreatic islets in our model. Adult F3 LowerB and UpperB male offspring had increased body weight relative to Controls, however glucose tolerance was similar in the three groups. F3 LowerB, but not UpperB, males had reduced β-cell mass and smaller islets which was associated with increased glucose-stimulated insulin secretion. Similar to F1 and F2 BPA male offspring, staining for markers of T-cells and macrophages (CD3 and F4/80) was increased in pancreas of F3 LowerB and UpperB male offspring, which was associated with changes in cytokine levels. In contrast to F3 BPA males, LowerB and UpperB female offspring had comparable body weight, glucose tolerance and insulin secretion as Controls. Thus, maternal BPA exposure resulted in fewer metabolic defects in F3 than F1 and F2 offspring, and these were sex- and dose-specific.

Keywords: endocrine disruptors; inflammation; insulin secretion; islets; transgenerational; β-cell mass.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Air Pollutants / toxicity*
  • Animals
  • Benzhydryl Compounds / toxicity*
  • Body Weight
  • Disease Models, Animal
  • Endocrine Disruptors / toxicity*
  • Female
  • Glucose Intolerance / diagnosis
  • Glucose Intolerance / etiology*
  • Glucose Tolerance Test
  • Humans
  • Insulin / metabolism
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism
  • Male
  • Maternal Exposure / adverse effects*
  • Mice
  • Mice, Inbred C57BL
  • Phenols / toxicity*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / diagnosis
  • Prenatal Exposure Delayed Effects / etiology*
  • Sex Factors

Substances

  • Air Pollutants
  • Benzhydryl Compounds
  • Endocrine Disruptors
  • Insulin
  • Phenols
  • bisphenol A