title: DNA methylation changes in whole blood is associated with exposure to the environmental contaminants, mercury, lead, cadmium and bisphenol A, in women undergoing ovarian stimulation for IVF.
abstract: BACKGROUND
  Changes in DNA methylation may play an important role in the deleterious reproductive effects reported in association with exposure to environmental pollutants. In this pilot study, we identify candidate methylation changes associated with exposure to pollutants in women undergoing in vitro fertilization (IVF).
  
  
  METHODS
  Blood and urine were collected from women on the day of oocyte retrieval. Whole blood was analyzed for mercury and lead, and urine for cadmium using inductively coupled plasma mass spectrometry. Unconjugated bisphenol A (BPA) was analyzed in serum using high-performance liquid chromatography with Coularray detection. Participants were dichotomized as higher or lower exposure groups by median concentrations. Using the Illumina GoldenGate Methylation Cancer Panel I, DNA methylation in whole blood from 43 women was assessed at 1505 CpG sites for association with exposure levels of each pollutant. Candidate CpG sites were identified using a Diff Score >|13| (P< 0.05) and an absolute difference >10% which were confirmed using bisulfite pyrosequencing.
  
  
  RESULTS
  Methylation of the GSTM1/5 promoter was increased for women with higher mercury exposure (P= 0.04); however, no correlation was observed (r= 0.17, P= 0.27). Reduced methylation was detected in the COL1A2 promoter in women with higher exposure to lead (P= 0.004), and an inverse correlation was observed (r = - 0.45, P= 0.03). Lower methylation of a promoter CpG site at the TSP50 gene was detected in women with higher BPA exposure (P= 0.005), and again an inverse correlation was identified (r = - 0.51, P= 0.001).
  
  
  CONCLUSIONS
  Altered DNA methylation at various CpG sites was associated with exposure to mercury, lead or BPA, providing candidates to be investigated using a larger study sample, as the results may reflect an independently associated predictor (e.g. socioeconomic status, diet, genetic variants, altered blood cell composition). Further studies accommodating variations in these factors will be needed to confirm these associations and identify their underlying causes.
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
authors.forename: Courtney W
authors.initials: CW
authors.lastname: Hanna
authors.forename: Michael S
authors.initials: MS
authors.lastname: Bloom
authors.forename: Wendy P
authors.initials: WP
authors.lastname: Robinson
authors.forename: Dongsul
authors.initials: D
authors.lastname: Kim
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Parsons
authors.forename: Frederick S
authors.initials: FS
authors.lastname: vom Saal
authors.forename: Julia A
authors.initials: JA
authors.lastname: Taylor
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Steuerwald
authors.forename: Victor Y
authors.initials: VY
authors.lastname: Fujimoto
mesh_terms: D000328:Adult; D001559:Benzhydryl Compounds / Q000097:blood / Q000633:toxicity; D001822:Body Burden; D002104:Cadmium / Q000633:toxicity / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000097:blood / Q000737:chemistry; D019175:DNA Methylation; D004785:Environmental Pollutants / Q000032:analysis* / Q000097:blood / Q000652:urine; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D007854:Lead / Q000097:blood / Q000633:toxicity; D018811:Maternal Exposure; D008628:Mercury / Q000097:blood / Q000633:toxicity; D010062:Ovulation Induction; D010636:Phenols / Q000097:blood / Q000633:toxicity; D010865:Pilot Projects; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D002104:Cadmium; D004247:DNA; D004785:Environmental Pollutants; D007854:Lead; D008628:Mercury; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds