Sex-specific epigenetic gene activation profiles are differentially modulated in human placentas affected by intrauterine growth restriction

J Reprod Immunol. 2020 Jun:139:103124. doi: 10.1016/j.jri.2020.103124. Epub 2020 Mar 25.

Abstract

Background: The purpose of this study was to investigate the sex specific expression of histone protein modifications responsible for rapid gene expression in IUGR placentas.

Patients and methods: We screened for fetal sex-specific expression of the histone proteins H3K4me3 and H3K9ac in 23 IUGR and 40 control placentas via immunohistochemistry. The trophoblast-like cell line BeWo was used in order to analyze a potential effect of stimulation with prednisolone on H3K4me3 and H3K9ac in vitro. Calculating regression models with additional adjustment for potential confounders were used.

Results: A significantly decreased level of H3K4me3 was detectable in female syncytiotrophoblasts, whereas H3K9ac was reduced predominantly in male extravillous throphoblast (EVT). No association to the gestational age existed.

Conclusion: Our data showed a reduced expression of the histone proteins H3K4me3 (female) and H3K9ac (male) in IUGR, furthermore elevated cortisol levels may lead to a sex-specific down-regulation of histone proteins in IUGR placentas.

Keywords: H3K4me3; H3K9ac; Histone modification.

MeSH terms

  • Adult
  • Cell Line
  • Epigenesis, Genetic
  • Female
  • Fetal Growth Retardation / genetics*
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • Male
  • Placenta / physiology*
  • Prednisolone / metabolism
  • Pregnancy
  • Regression Analysis
  • Sex*
  • Trophoblasts / physiology*

Substances

  • Histones
  • histone H3 trimethyl Lys4
  • Prednisolone