Prenatal exposure to di-(2-ethylhexyl) phthalate and high-fat diet synergistically disrupts mouse fetal oogenesis and affects folliculogenesis†

Biol Reprod. 2019 Jun 1;100(6):1561-1570. doi: 10.1093/biolre/ioz051.

Abstract

Di-(2-ethylhexyl) phthalate (DEHP) is a chemical that is widely used as a plasticizer. Exposure to DEHP has been shown to alter ovarian function in humans. Additionally, foods high in fat content, regularly found in the western diet, have been shown to be another potential disruptor of fetal ovarian function. Due to DEHP's lipophilicity, high-fat foods can be easily contaminated. Therefore, exposure to DEHP and a high-fat diet are both health concerns, especially in pregnant women, and the effects of these exposures on fetal oocyte quality and quantity should be elucidated. In this study, our goal was to determine if there are synergistic effects of DEHP exposure at an environmentally relevant level (20 μg/kg body weight/day) and high-fat diet on oogenesis and folliculogenesis. Dams were fed with a high-fat diet (45 kcal% fat) or a control diet (10 kcal% fat) 1 week before mating and during pregnancy and lactation. The pregnant mice were dosed with DEHP (20 μg/kg body weight/day) or vehicle control from E10.5 to litter birth. We found that treatment with an environmentally relevant dosage of DEHP and consumption of high-fat diet significantly increases synapsis defects in meiosis and affects folliculogenesis in the F1 generation.

Keywords: fertility; follicular development; meiosis; meiotic silencing of unsynapsed chromatin (MSUC); multigenerational effect; synapsis.

Publication types

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

MeSH terms

  • Animals
  • Diet, High-Fat / adverse effects*
  • Dietary Fats / pharmacology
  • Diethylhexyl Phthalate / toxicity*
  • Drug Synergism
  • Endocrine Disruptors / toxicity
  • Female
  • Fetus / drug effects*
  • Gene Expression Regulation, Developmental / drug effects
  • Gene Silencing / drug effects
  • Maternal Exposure / adverse effects
  • Maternal Nutritional Physiological Phenomena
  • Meiosis / drug effects
  • Meiosis / genetics
  • Mice
  • Oogenesis / drug effects*
  • Oogenesis / physiology
  • Ovarian Follicle / drug effects*
  • Ovarian Follicle / physiology
  • Pregnancy
  • Prenatal Exposure Delayed Effects / etiology
  • Prenatal Exposure Delayed Effects / genetics
  • Prenatal Exposure Delayed Effects / physiopathology*

Substances

  • Dietary Fats
  • Endocrine Disruptors
  • Diethylhexyl Phthalate