title: Prenatal exposure to mixtures of xenoestrogens and repetitive element DNA methylation changes in human placenta.
abstract: BACKGROUND
  Prenatal exposure to endocrine disrupting compounds (EDCs) has previously shown to alter epigenetic marks.
  
  
  OBJECTIVE
  In this work we explore whether prenatal exposure to mixtures of xenoestrogens has the potential to alter the placenta epigenome, by studying DNA methylation in retrotransposons as a surrogate of global DNA methylation.
  
  
  METHODS
  The biomarker total effective xenoestrogen burden (TEXB) was measured in 192 placentas from participants in the longitudinal INMA Project. DNA methylation was quantitatively assessed by bisulfite pyrosequencing on 10 different retrotransposons including 3 different long interspersed nuclear elements (LINEs), 4 short interspersed nuclear elements (SINEs) and 3 human endogenous retroviruses (HERVs). Associations were tested using linear mixed-effects regression models and sex interaction was evaluated.
  
  
  RESULTS
  A significant sex interaction was observed for AluYb8 (p-value for interaction <0.001, significant at Bonferroni corrected p-value threshold of 0.0025). Boys with the highest TEXB-alpha levels of exposure (third tertile) presented on average a decrease of 0.84% in methylation compared to those in the first tertile (p-value<0.001), while no significant effects were found in girls (p-value=0.134).
  
  
  CONCLUSIONS
  Our findings suggest that boys may be more susceptible to the effect of exposure to xenoestrogens during prenatal development, producing shifts in DNA methylation of certain sensitive genomic repetitive sequences in a tissue important for fetal growth and development.
authors: Center for Research in Environmental Epidemiology (CREAL), Barcelona, Catalonia, Spain; Hospital del Mar Medical Research Institute (IMIM), Barcelona, Catalonia, Spain; Genomics and Disease Group, Bioinformatics and Genomics Program, Center for Genomic Regulation (CRG), Barcelona, Catalonia, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Spain. Electronic address: nvilahur@creal.cat.
authors: Nadia
authors: N
authors: Vilahur
authors: Center for Research in Environmental Epidemiology (CREAL), Barcelona, Catalonia, Spain; Hospital del Mar Medical Research Institute (IMIM), Barcelona, Catalonia, Spain; Genomics and Disease Group, Bioinformatics and Genomics Program, Center for Genomic Regulation (CRG), Barcelona, Catalonia, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Spain.
authors: Mariona
authors: M
authors: Bustamante
authors: Laboratory of Environmental Epigenetics, Exposure Epidemiology and Risk Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA.
authors: Hyang-Min
authors: HM
authors: Byun
authors: Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Spain; Department of Radiology, Centro de Investigación Biomédica, University of Granada, Granada, Spain; Instituto de Investigación Biosanitaria de Granada, Hospital Universitario San Cecilio, Granada, Spain.
authors: Mariana F
authors: MF
authors: Fernandez
authors: Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Spain; Subdirección de Salud Pública de Gipuzkoa, Department of Health of the Basque, Spain; Health Research Institute, BIODONOSTIA, Basque Country, Spain.
authors: Loreto
authors: L
authors: Santa Marina
authors: Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Spain; Subdirección de Salud Pública de Gipuzkoa, Department of Health of the Basque, Spain; Health Research Institute, BIODONOSTIA, Basque Country, Spain.
authors: Mikel
authors: M
authors: Basterrechea
authors: Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Spain; Centre for Public Health Research (CSISP-FISABIO), Valencia, Spain; University of Valencia, Valencia, Spain.
authors: Ferran
authors: F
authors: Ballester
authors: Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Spain; Centre for Public Health Research (CSISP-FISABIO), Valencia, Spain; University of Valencia, Valencia, Spain.
authors: Mario
authors: M
authors: Murcia
authors: Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Spain; University of Oviedo, Oviedo, Asturias, Spain.
authors: Adonina
authors: A
authors: Tardón
authors: Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Spain; University of Oviedo, Oviedo, Asturias, Spain.
authors: Ana
authors: A
authors: Fernández-Somoano
authors: Hospital del Mar Medical Research Institute (IMIM), Barcelona, Catalonia, Spain; Genomics and Disease Group, Bioinformatics and Genomics Program, Center for Genomic Regulation (CRG), Barcelona, Catalonia, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Spain; Department of Health and Life Sciences, University Pompeu Fabra (UPF), Barcelona, Catalonia, Spain.
authors: Xavier
authors: X
authors: Estivill
authors: Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Spain; Department of Radiology, Centro de Investigación Biomédica, University of Granada, Granada, Spain; Instituto de Investigación Biosanitaria de Granada, Hospital Universitario San Cecilio, Granada, Spain.
authors: Nicolas
authors: N
authors: Olea
authors: Center for Research in Environmental Epidemiology (CREAL), Barcelona, Catalonia, Spain; Hospital del Mar Medical Research Institute (IMIM), Barcelona, Catalonia, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Spain; Department of Health and Life Sciences, University Pompeu Fabra (UPF), Barcelona, Catalonia, Spain.
authors: Jordi
authors: J
authors: Sunyer
authors: Laboratory of Environmental Epigenetics, Exposure Epidemiology and Risk Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA.
authors: Andrea A
authors: AA
authors: Baccarelli
mesh_terms: D000328:Adult; D001822:Body Burden; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D019175:DNA Methylation / Q000187:drug effects*; D052244:Endocrine Disruptors / Q000378:metabolism / Q000633:toxicity*; D004785:Environmental Pollutants / Q000378:metabolism / Q000633:toxicity*; D004967:Estrogens / Q000633:toxicity*; D005260:Female; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000187:drug effects* / Q000235:genetics; D008137:Longitudinal Studies; D008297:Male; D018811:Maternal Exposure; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D012044:Regression Analysis; D012737:Sex Factors; D013030:Spain; D018709:Statistics, Nonparametric
chemical_list: D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D004967:Estrogens
keywords: Biomarker; Global DNA methylation; Placenta; Sex; TEXB; Xenoestrogens