Epigenetic transgenerational inheritance of vinclozolin induced mouse adult onset disease and associated sperm epigenome biomarkers

Reprod Toxicol. 2012 Dec;34(4):694-707. doi: 10.1016/j.reprotox.2012.09.005. Epub 2012 Oct 2.


The endocrine disruptor vinclozolin has previously been shown to promote epigenetic transgenerational inheritance of adult onset disease in the rat. The current study was designed to investigate the transgenerational actions of vinclozolin on the mouse. Transient exposure of the F0 generation gestating female during gonadal sex determination promoted transgenerational adult onset disease in F3 generation male and female mice, including spermatogenic cell defects, testicular abnormalities, prostate abnormalities, kidney abnormalities and polycystic ovarian disease. Pathology analysis demonstrated 75% of the vinclozolin lineage animals developed disease with 34% having two or more different disease states. Interestingly, the vinclozolin induced transgenerational disease was observed in the outbred CD-1 strain, but not the inbred 129 mouse strain. Analysis of the F3 generation sperm epigenome identified differential DNA methylation regions that can potentially be utilized as epigenetic biomarkers for transgenerational exposure and disease.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Androgen Antagonists / administration & dosage
  • Androgen Antagonists / toxicity*
  • Animals
  • Animals, Outbred Strains
  • Apoptosis / drug effects
  • Biomarkers
  • DNA Methylation
  • Endocrine Disruptors / administration & dosage
  • Endocrine Disruptors / toxicity*
  • Epigenesis, Genetic*
  • Epigenomics
  • Female
  • Flutamide / toxicity
  • Kidney / drug effects
  • Kidney / pathology
  • Male
  • Mice
  • Mice, Inbred Strains
  • Ovarian Cysts / chemically induced
  • Oxazoles / administration & dosage
  • Oxazoles / toxicity*
  • Pregnancy
  • Prostate / drug effects
  • Prostate / pathology
  • Sperm Motility / drug effects
  • Testis / drug effects
  • Testis / pathology


  • Androgen Antagonists
  • Biomarkers
  • Endocrine Disruptors
  • Oxazoles
  • Flutamide
  • vinclozolin