Sexually Dimorphic Effects of Early-Life Exposures to Endocrine Disruptors: Sex-Specific Epigenetic Reprogramming as a Potential Mechanism

Curr Environ Health Rep. 2017 Dec;4(4):426-438. doi: 10.1007/s40572-017-0170-z.


Purpose of review: The genetic material of every organism exists within the context of regulatory networks that govern gene expression-collectively called the epigenome. Animal models and human birth cohort studies have revealed key developmental periods that are important for epigenetic programming and vulnerable to environmental insults. Thus, epigenetics represent a potential mechanism through which sexually dimorphic effects of early-life exposures such as endocrine-disrupting chemicals (EDCs) manifest.

Recent findings: Several animal studies, and to a lesser extent human studies, have evaluated life-course sexually dimorphic health effects following developmental toxicant exposures; many fewer studies, however, have evaluated epigenetics as a mechanism mediating developmental exposures and later outcomes. To evaluate epigenetic reprogramming as a mechanistic link of sexually dimorphic early-life EDCs exposures, the following criteria should be met: (1) well-characterized exposure paradigm that includes relevant windows for developmental epigenetic reprogramming; (2) evaluation of sex-specific exposure-related epigenetic change; and (3) observation of a sexually dimorphic phenotype in either childhood, adolescence, or adulthood.

Keywords: Bisphenol A (BPA); Developmental origins of health and disease (DOHaD); Epigenetics; Lead (Pb); Sexually dimorphic effects.

Publication types

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

MeSH terms

  • Animals
  • Benzhydryl Compounds / toxicity
  • DNA Methylation / drug effects
  • Endocrine Disruptors / adverse effects*
  • Epigenesis, Genetic / drug effects*
  • Female
  • Humans
  • Lead / toxicity
  • Phenols / toxicity
  • Pregnancy
  • Prenatal Exposure Delayed Effects / genetics*


  • Benzhydryl Compounds
  • Endocrine Disruptors
  • Phenols
  • Lead
  • bisphenol A