Vinclozolin induced epigenetic transgenerational inheritance of pathologies and sperm epimutation biomarkers for specific diseases

PLoS One. 2018 Aug 29;13(8):e0202662. doi: 10.1371/journal.pone.0202662. eCollection 2018.

Abstract

Exposure to vinclozolin has been shown to induce the epigenetic transgenerational inheritance of increased susceptibility to disease, and to induce transgenerational changes to the epigenome. In the current study, gestating F0 generation rats were exposed to vinclozolin, and the subsequent F1, F2 and transgenerational F3 generations were evaluated for diseases and pathologies. F1 and F2 generation rats exhibited few abnormalities. However, F3 generation rats showed transgenerational increases in testis, prostate, and kidney disease, changes in the age of puberty onset in males, and an increased obesity rate in females. Overall there was an increase in the rate of animals with disease, and in the incidence of animals with multiple diseases. The objective of the current study was to analyze the sperm epigenome of F3 generation rats with specific abnormalities and compare them to rats without those abnormalities, in an effort to find epigenetic biomarkers of transgenerational disease. Unique signatures of differential DNA methylation regions (DMRs) in sperm were found that associated with testis disease, prostate disease and kidney disease. Confounding factors identified were the presence of multiple diseases in the analysis and the limited number of animals without disease. These results further our understanding of the mechanisms governing epigenetic transgenerational inheritance, and may lead in the future to the use of epigenetic biomarkers that will help predict an individual's susceptibility for specific diseases.

Publication types

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

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Biomarkers / metabolism*
  • Chromosome Mapping
  • Chromosomes / genetics
  • Chromosomes / metabolism
  • DNA Methylation
  • Epigenesis, Genetic / drug effects*
  • Female
  • Fungicides, Industrial / toxicity*
  • Heredity / genetics
  • Kidney Diseases / etiology
  • Kidney Diseases / genetics
  • Kidney Diseases / pathology
  • Male
  • Oxazoles / toxicity*
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Prostatic Diseases / etiology
  • Prostatic Diseases / genetics
  • Prostatic Diseases / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Spermatozoa / drug effects*
  • Spermatozoa / metabolism
  • Testis / pathology

Substances

  • Biomarkers
  • Fungicides, Industrial
  • Oxazoles
  • vinclozolin

Grant support

This study was supported by a John Templeton Foundation (50183) (https://www.templeton.org/) grant to MKS and NIH (ES012974) (https://www.nih.gov/) grant to MKS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.