Sexual epigenetic dimorphism in the human placenta: implications for susceptibility during the prenatal period

Epigenomics. 2017 Mar;9(3):267-278. doi: 10.2217/epi-2016-0132. Epub 2017 Feb 17.


Aim: 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.

Methods: 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.

Results: 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.

Conclusion: These data highlight sex-dependent epigenetic patterning in the placenta and provide insight into differences in infant outcomes and responses to the perinatal environment.

Keywords: CpG DNA methylation; epigenetics; placenta; sexual dimorphism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • CpG Islands
  • DNA Methylation*
  • Epigenesis, Genetic*
  • Female
  • Genome, Human
  • Humans
  • Infant, Extremely Premature / blood*
  • Infant, Newborn
  • Male
  • Placenta / metabolism
  • Pregnancy
  • Premature Birth / blood
  • Premature Birth / genetics*
  • Sex Factors