title: Sexual epigenetic dimorphism in the human placenta: implications for susceptibility during the prenatal period.
abstract: Sex-based differences in response to adverse prenatal environments and infant outcomes have been observed, yet the underlying mechanisms for this are unclear. The placental epigenome may be a driver of these differences.
  
  
  
  Placental DNA methylation was assessed at more than 480,000 CpG sites from male and female infants enrolled in the extremely low gestational age newborns cohort (ELGAN) and validated in a separate US-based cohort. The impact of gestational age on placental DNA methylation was further examined using the New Hampshire Birth Cohort Study for a total of n = 467 placentas.
  
  
  
  A total of n = 2745 CpG sites, representing n = 587 genes, were identified as differentially methylated (p < 1 × 10-7). The majority (n = 582 or 99%) of these were conserved among the New Hampshire Birth Cohort. The identified genes encode proteins related to immune function, growth/transcription factor signaling and transport across cell membranes.
  
  
  
  These data highlight sex-dependent epigenetic patterning in the placenta and provide insight into differences in infant outcomes and responses to the perinatal environment.
authors.affiliation: Department of Environmental Sciences & Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Martin
authors.affiliation: Department of Environmental Sciences & Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Smeester
authors.affiliation: Department of Environmental Sciences & Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Paige A
authors.initials: PA
authors.lastname: Bommarito
authors.affiliation: Department of Obstetrics & Gynecology, University of North Carolina School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Grace
authors.affiliation: Department of Obstetrics & Gynecology, University of North Carolina School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Kim
authors.initials: K
authors.lastname: Boggess
authors.affiliation: Department of Pediatrics, Boston Medical Center, Boston, MA, USA.
authors.forename: Karl
authors.initials: K
authors.lastname: Kuban
authors.affiliation: Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Karagas
authors.affiliation: Department of Environmental Health, Rollins School of Public Health at Emory University, Atlanta, GA 30322, USA.
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Marsit
authors.affiliation: Department of Pediatrics, University of North Carolina School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: T Michael
authors.initials: TM
authors.lastname: O'Shea
authors.affiliation: Department of Environmental Sciences & Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Fry
mesh_terms: D000293:Adolescent; D000328:Adult; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015894:Genome, Human; D006801:Humans; D062071:Infant, Extremely Premature / Q000097:blood*; D007231:Infant, Newborn; D008297:Male; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D047928:Premature Birth / Q000097:blood / Q000235:genetics*; D012737:Sex Factors
keywords: CpG DNA methylation; epigenetics; placenta; sexual dimorphism