Multigenerational and transgenerational effects of endocrine disrupting chemicals: A role for altered epigenetic regulation?

Semin Cell Dev Biol. 2015 Jul;43:66-75. doi: 10.1016/j.semcdb.2015.05.008. Epub 2015 May 28.


Increasing evidence has highlighted the critical role of early life environment in shaping the future health outcomes of an individual. Moreover, recent studies have revealed that early life perturbations can affect the health of subsequent generations. Hypothesized mechanisms of multi- and transgenerational inheritance of abnormal developmental phenotypes include epigenetic misregulation in germ cells. In this review, we will focus on the available data demonstrating the ability of endocrine disrupting chemicals (EDCs), including bisphenol A (BPA), phthalates, and parabens, to alter epigenetic marks in rodents and humans. These epigenetic marks include DNA methylation, histone post-translational modifications, and non-coding RNAs. We also review the current evidence for multi- and transgenerational inheritance of abnormal developmental changes in the offspring following EDC exposure. Based on published results, we conclude that EDC exposure can alter the mouse and human epigenome, with variable tissue susceptibilities. Although increasing data suggest that exposure to EDCs is linked to transgenerational inheritance of reproductive, metabolic, or neurological phenotypes, more studies are needed to validate these observations and to elucidate further whether these developmental changes are directly associated with the relevant epigenetic alterations.

Keywords: Bisphenol A; Endocrine disrupting chemicals; Epigenetics; Parabens; Phthalates; Transgenerational inheritance.

Publication types

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

MeSH terms

  • Animals
  • Benzhydryl Compounds / adverse effects
  • Benzhydryl Compounds / pharmacology*
  • DNA Methylation / drug effects
  • DNA Methylation / genetics
  • Endocrine Disruptors / adverse effects
  • Endocrine Disruptors / pharmacology*
  • Epigenesis, Genetic / drug effects*
  • Epigenesis, Genetic / genetics
  • Humans
  • Inheritance Patterns / drug effects*
  • Mice
  • Parabens / adverse effects
  • Parabens / pharmacology*
  • Phenols / adverse effects
  • Phenols / pharmacology*
  • Phenotype
  • Phthalic Acids / adverse effects
  • Phthalic Acids / pharmacology*
  • Protein Processing, Post-Translational / drug effects
  • Protein Processing, Post-Translational / genetics
  • RNA, Untranslated / drug effects
  • RNA, Untranslated / genetics


  • Benzhydryl Compounds
  • Endocrine Disruptors
  • Parabens
  • Phenols
  • Phthalic Acids
  • RNA, Untranslated
  • phthalic acid
  • bisphenol A