Exposure to the environmental endocrine disruptor TCDD and human reproductive dysfunction: Translating lessons from murine models

Reprod Toxicol. 2017 Mar;68:59-71. doi: 10.1016/j.reprotox.2016.07.007. Epub 2016 Jul 14.

Abstract

Humans and other animals are exposed to a wide array of man-made toxicants, many of which act as endocrine disruptors that exhibit differential effects across the lifespan. In humans, while the impact of adult exposure is known for some compounds, the potential consequences of developmental exposure to endocrine disrupting chemicals (EDCs) is more difficult to ascertain. Animal studies have revealed that exposure to EDCs prior to puberty can lead to adult reproductive disease and dysfunction. Specifically, in adult female mice with an early life exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), we demonstrated a transgenerational occurrence of several reproductive diseases that have been linked to endometriosis in women. Herein, we review the evidence for TCDD-associated development of adult reproductive disease as well as known epigenetic alterations associated with TCDD and/or endometriosis. We will also introduce new "Organ-on-Chip" models which, combined with our established murine model, are expected to further enhance our ability to examine alterations in gene-environment interactions that lead to heritable disease.

Keywords: Adenomyosis; Endometriosis; Epigenetics; Preterm birth; TCDD; Transgenerational.

Publication types

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

MeSH terms

  • Animals
  • Endocrine Disruptors / toxicity*
  • Endometriosis / chemically induced
  • Endometriosis / genetics
  • Environmental Exposure / adverse effects*
  • Epigenesis, Genetic / drug effects
  • Female
  • Humans
  • Male
  • Mice
  • Polychlorinated Dibenzodioxins / toxicity*
  • Reproduction / drug effects*
  • Reproduction / genetics

Substances

  • Endocrine Disruptors
  • Polychlorinated Dibenzodioxins