Metabolic disruption in male mice due to fetal exposure to low but not high doses of bisphenol A (BPA): evidence for effects on body weight, food intake, adipocytes, leptin, adiponectin, insulin and glucose regulation

Reprod Toxicol. 2013 Dec;42:256-68. doi: 10.1016/j.reprotox.2013.07.017. Epub 2013 Jul 25.

Abstract

Exposure to bisphenol A (BPA) is implicated in many aspects of metabolic disease in humans and experimental animals. We fed pregnant CD-1 mice BPA at doses ranging from 5 to 50,000μg/kg/day, spanning 10-fold below the reference dose to 10-fold above the currently predicted no adverse effect level (NOAEL). At BPA doses below the NOAEL that resulted in average unconjugated BPA between 2 and 200pg/ml in fetal serum (AUC0-24h), we observed significant effects in adult male offspring: an age-related change in food intake, an increase in body weight and liver weight, abdominal adipocyte mass, number and volume, and in serum leptin and insulin, but a decrease in serum adiponectin and in glucose tolerance. For most of these outcomes non-monotonic dose-response relationships were observed; the highest BPA dose did not produce a significant effect for any outcome. A 0.1-μg/kg/day dose of DES resulted in some but not all low-dose BPA outcomes.

Keywords: Adipocytes; Endocrine disruption; Food intake; Glucose tolerance; Metabolic syndrome.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Abdominal Fat / drug effects
  • Adipocytes / cytology
  • Adipocytes / drug effects
  • Adiponectin / blood
  • Animals
  • Benzhydryl Compounds / blood
  • Benzhydryl Compounds / pharmacokinetics
  • Benzhydryl Compounds / toxicity*
  • Body Weight / drug effects
  • Cell Count
  • Cell Size
  • Eating / drug effects
  • Endocrine Disruptors / blood
  • Endocrine Disruptors / pharmacokinetics
  • Endocrine Disruptors / toxicity*
  • Female
  • Glucose / metabolism
  • Glucose Tolerance Test
  • Insulin / blood
  • Leptin / blood
  • Male
  • Maternal-Fetal Exchange
  • Mice
  • Phenols / blood
  • Phenols / pharmacokinetics
  • Phenols / toxicity*
  • Pregnancy

Substances

  • Adiponectin
  • Benzhydryl Compounds
  • Endocrine Disruptors
  • Insulin
  • Leptin
  • Phenols
  • Glucose
  • bisphenol A