title: Chronic exposure to a low concentration of bisphenol A during follicle culture affects the epigenetic status of germinal vesicles and metaphase II oocytes.
abstract: OBJECTIVE
  To determine whether exposure to low concentrations of the endocrine disrupting chemical bisphenol A (BPA) during follicle culture and oocyte growth alters the methylation status of differentially methylated regions (DMRs) of imprinted genes and histone posttranslational modification patterns in mammalian oocytes.
  
  
  METHODS
  Comparative and control study.
  
  
  METHODS
  Experimental laboratory.
  
  
  METHODS
  C57/Bl6JxCBA/Ca mice.
  
  
  METHODS
  Exposure of oocytes to 3 nM or 300 nM BPA during follicle culture from preantral to antral stage.
  
  
  METHODS
  Methylation status of DMRs of maternally imprinted (Snrpn, Igf2r, and Mest) and paternally imprinted gene(s) (H19) in mouse germinal vesicle oocytes; trimethylation of histone H3K9, acetylation of histone H4K12, and distance between centromeres of sister chromatids in metaphase II oocytes.
  
  
  RESULTS
  Exposure to 3 nM BPA was associated with slightly accelerated follicle development, statistically significant increases in allele methylation errors in DMRs of maternally imprinted genes, and statistically significant decreases in histone H3K9 trimethylation and interkinetochore distance.
  
  
  CONCLUSIONS
  The disturbances in oocyte genomic imprinting and modification of posttranslational histone and centromere architecture provide the first link between low BPA exposures and induction of epigenetic changes that may contribute to chromosome congression failures and meiotic errors, and to altered gene expression that might affect health of the offspring.
authors.affiliation: Institute of Gene Technology/Microbiology, University of Bielefeld, Bielefeld, Germany.
authors.forename: Tom
authors.initials: T
authors.lastname: Trapphoff
authors.forename: Martyna
authors.initials: M
authors.lastname: Heiligentag
authors.forename: Nady
authors.initials: N
authors.lastname: El Hajj
authors.forename: Thomas
authors.initials: T
authors.lastname: Haaf
authors.forename: Ursula
authors.initials: U
authors.lastname: Eichenlaub-Ritter
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000008:administration & dosage*; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000187:drug effects*; D004785:Environmental Pollutants / Q000008:administration & dosage; D044127:Epigenesis, Genetic / Q000187:drug effects / Q000502:physiology*; D005260:Female; D008677:Metaphase / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009865:Oocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D006080:Ovarian Follicle / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D010636:Phenols / Q000008:administration & dosage*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D004785:Environmental Pollutants; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Aneuploidy; BPA; histone methylation; imprint pattern; oocyte