Perinatal exposure to a human relevant mixture of persistent organic pollutants: Effects on mammary gland development, ovarian folliculogenesis and liver in CD-1 mice

PLoS One. 2021 Jun 10;16(6):e0252954. doi: 10.1371/journal.pone.0252954. eCollection 2021.

Abstract

The ability of persistent organic pollutants (POPs) with endocrine disrupting properties to interfere with the developing reproductive system is of increasing concern. POPs are transferred from dams to offspring and the high sensitivity of neonates to endocrine disturbances may be caused by underdeveloped systems of metabolism and excretion. The present study aimed to characterize the effect of in utero and lactational exposure to a human relevant mixture of POPs on the female mammary gland, ovarian folliculogenesis and liver function in CD-1 offspring mice. Dams were exposed to the mixture through the diet at Control, Low or High doses (representing 0x, 5000x and 100 000x human estimated daily intake levels, respectively) from weaning and throughout mating, gestation, and lactation. Perinatally exposed female offspring exhibited altered mammary gland development and a suppressed ovarian follicle maturation. Increased hepatic cytochrome P450 enzymatic activities indirectly indicated activation of nuclear receptors and potential generation of reactive products. Hepatocellular hypertrophy was observed from weaning until 30 weeks of age and could potentially lead to hepatotoxicity. Further studies should investigate the effects of human relevant mixtures of POPs on several hormones combined with female reproductive ability and liver function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytochrome P-450 Enzyme System / metabolism
  • Endocrine Disruptors / toxicity*
  • Female
  • Humans
  • Lactation / drug effects
  • Liver / drug effects
  • Liver / physiology*
  • Liver Function Tests
  • Mammary Glands, Animal / drug effects
  • Mammary Glands, Animal / growth & development*
  • Maternal Exposure / adverse effects*
  • Mice
  • Ovarian Follicle / drug effects
  • Ovarian Follicle / growth & development*
  • Persistent Organic Pollutants / toxicity*
  • Pregnancy
  • Up-Regulation

Substances

  • Endocrine Disruptors
  • Cytochrome P-450 Enzyme System

Grants and funding

The present study was funded by the Norwegian Research Council, Grant numbers 21307 and 204361 (ER). The funders played no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.