title: Deleterious effects of endocrine disruptors are corrected in the mammalian germline by epigenome reprogramming.
abstract: BACKGROUND
  Exposure to environmental endocrine-disrupting chemicals during pregnancy reportedly causes transgenerationally inherited reproductive defects. We hypothesized that to affect the grandchild, endocrine-disrupting chemicals must alter the epigenome of the germ cells of the in utero-exposed G1 male fetus. Additionally, to affect the great-grandchild, the aberration must persist in the germ cells of the unexposed G2 grandchild.
  
  
  RESULTS
  Here, we treat gestating female mice with vinclozolin, bisphenol A, or di-(2-ethylhexyl)phthalate during the time when global de novo DNA methylation and imprint establishment occurs in the germ cells of the G1 male fetus. We map genome-wide features in purified G1 and G2 prospermatogonia, in order to detect immediate and persistent epigenetic aberrations, respectively. We detect changes in transcription and methylation in the G1 germline immediately after endocrine-disrupting chemicals exposure, but changes do not persist into the G2 germline. Additional analysis of genomic imprints shows no persistent aberrations in DNA methylation at the differentially methylated regions of imprinted genes between the G1 and G2 prospermatogonia, or in the allele-specific transcription of imprinted genes between the G2 and G3 soma.
  
  
  CONCLUSIONS
  Our results suggest that endocrine-disrupting chemicals exert direct epigenetic effects in exposed fetal germ cells, which are corrected by reprogramming events in the next generation. Avoiding transgenerational inheritance of environmentally-caused epigenetic aberrations may have played an evolutionary role in the development of dual waves of global epigenome reprogramming in mammals.
authors: Khursheed
authors: K
authors: Iqbal
authors: Diana A
authors: DA
authors: Tran
authors: Arthur X
authors: AX
authors: Li
authors: Charles
authors: C
authors: Warden
authors: Angela Y
authors: AY
authors: Bai
authors: Purnima
authors: P
authors: Singh
authors: Xiwei
authors: X
authors: Wu
authors: Gerd P
authors: GP
authors: Pfeifer
authors: Piroska E
authors: PE
authors: Szabó
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000008:administration & dosage; D065150:Cellular Reprogramming / Q000187:drug effects / Q000235:genetics*; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics*; D052244:Endocrine Disruptors / Q000008:administration & dosage; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005260:Female; D018392:Genomic Imprinting / Q000187:drug effects* / Q000235:genetics; D005854:Germ Cells / Q000187:drug effects; D008297:Male; D051379:Mice; D010080:Oxazoles / Q000008:administration & dosage; D010636:Phenols / Q000008:administration & dosage; D011247:Pregnancy; D012098:Reproduction / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D010080:Oxazoles; D010636:Phenols; C025643:vinclozolin; C006780:bisphenol A; D000098826:Bisphenol A Compounds