title: [Genome-wide analysis of DNA methylation changes in the rat ovary after prenatal exposure to di-(2-ethylhexyl)-phthalate].
abstract: OBJECTIVE
  To study the effects of prenatal exposure to Di-(2-ethylhexyl)-phthalate (DEHP) on genome-wide epigenetic alterations in ovary of adult offspring rat.
  
  
  METHODS
  Pregnant Wistar rats were randomly treated with DEHP (1000 mg/kg) or con oil at 12 - 17 days upon pregnance. DNA methylation changes in the ovary for the adult offsprings which were 70 days old were detected by Rat DNA methylation promoter plus CpG island arrays CpG island chip. Gene ontology (GO) method was performed to analyze the function of genes which were significantly different between exposed group and control group. Gene Igfbp1 (insulin-like growth factor binding protein 1) and Itga3 (integrin alpha 3) were randomly selected and the methylation status were verified by bisulfite genomic sequencing (BSP).
  
  
  RESULTS
  The methylation status were significantly different between exposed and control group in 406 genes (71 genes as hypermethylation and 335 genes as hypomethylation) (P < 0.05). GO analysis revealed that molecular transducer activity, cell part, cell, cellular process, multicellular organismal process, response to stimulus, biological regulation, regulation of biological process, reproduction, reproductive process, and rhythmic process were involved. The sequencing results were consistent with the data obtained by chips.
  
  
  CONCLUSIONS
  This study provides evidence that prenatal exposure of DEHP may be associated with methylation changes on the genes in the rat ovary. Genes related to reproductive process have highly significant methylation changes, which may shed new light on mechanisms of reproductive and developmental toxicity after prenatal exposure to DEHP.
authors.affiliation: Department of Environmental Health, School of Public Health, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xie
authors.forename: Yu
authors.initials: Y
authors.lastname: Gao
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Ding
authors.forename: Rong
authors.initials: R
authors.lastname: Shi
authors.forename: Yi-jun
authors.initials: YJ
authors.lastname: Zhou
authors.forename: Ying
authors.initials: Y
authors.lastname: Tian
mesh_terms: D000818:Animals; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D005260:Female; D016678:Genome; D018811:Maternal Exposure; D010053:Ovary / Q000473:pathology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004051:Diethylhexyl Phthalate