Prenatal exposure to bisphenol A at the reference dose impairs mitochondria in the heart of neonatal rats

J Appl Toxicol. 2014 Sep;34(9):1012-22. doi: 10.1002/jat.2924. Epub 2013 Sep 18.

Abstract

Bisphenol A (BPA) exposure has been reported to be epidemiologically associated with heart disease. As mitochondria play an important role in the early development of the heart and in the pathogenesis of heart disease, the current study investigated the possibility of cardiac mitochondrial injury in neonatal rat heart prenatally exposed to BPA. Pregnant Wistar rats were exposed to BPA 50 µg kg(-1) day(-1) or corn oil 1 ml kg(-1) by oral gavage throughout gestation. Heart samples from pups on postnatal day 1 were isolated for analysis. Ultrastructure results showed mild swelling with dissociation of cristae in myocardial mitochondria of BPA-treated rats. Additionally, mitochondrial membrane potential and the activity of respiratory chain complex II were significantly decreased. However, the activities of other three complexes (CI, CIII, CIV) and cardiac histology stayed normal. The expression levels of some key regulators involved in mitochondria energy metabolism and ATP-generating pathways were downregulated. The study demonstrated for the first time that prenatal exposure to BPA at the reference dose could impair mitochondria in the hearts of neonatal rats.

Keywords: BPA; heart; mitochondria dysfunction; prenatal exposure; reference dose.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzhydryl Compounds / administration & dosage*
  • Dose-Response Relationship, Drug
  • Energy Metabolism
  • Female
  • Gene Expression
  • Heart / drug effects*
  • Heart / physiopathology
  • Immunohistochemistry
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria, Heart / drug effects*
  • Mitochondria, Heart / pathology
  • Phenols / administration & dosage*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced
  • Prenatal Exposure Delayed Effects / physiopathology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Succinate Dehydrogenase / metabolism

Substances

  • Benzhydryl Compounds
  • Phenols
  • RNA, Messenger
  • Succinate Dehydrogenase
  • bisphenol A