Progesterone receptor B promoter hypermethylation in human placenta after labor onset

Reprod Sci. 2015 Mar;22(3):335-42. doi: 10.1177/1933719114542013. Epub 2014 Jul 11.

Abstract

To determine the methylation status of progesterone receptor B (PR-B) promoter and how PR-B regulates progesterone action in placenta during human pregnancy. Placentas were obtained from the pregnancy women at term who underwent cesarean delivery and vaginal delivery. The methylation status of the PR-B promoter was analyzed using the methylation-specific polymerase chain reaction (PCR) and bisulfite sequencing PCR. And the messenger RNA (mRNA) and protein expression of the PR-B and DNA methyltransferases (DNMTs) were determined by quantitative real-time PCR and Western blot. Compared with the cesarean group, the placentas of vaginal delivery group had greater levels of PR-B DNA methylation, and the PR-B, DNMT1, DNMT3a, and DNMT3b mRNA and protein expression were significantly decreased. Progesterone receptor B methylation occurs with high frequency after labor onset and may play an important epigenetic mechanism of labor-related PR-B negative expression, thereby mediating the biological process of functional progesterone withdrawal at term for parturition.

Keywords: DNA methylation; DNA methyltransferases; human parturition; placenta; progesterone receptor B.

MeSH terms

  • Adult
  • Blotting, Western
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Methylation*
  • DNA Methyltransferase 3A
  • DNA Methyltransferase 3B
  • Epigenesis, Genetic*
  • Female
  • Gene Expression Regulation
  • Humans
  • Labor, Obstetric / genetics*
  • Labor, Obstetric / metabolism
  • Pregnancy
  • Promoter Regions, Genetic*
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Receptors, Progesterone / genetics*
  • Receptors, Progesterone / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • DNMT3A protein, human
  • RNA, Messenger
  • Receptors, Progesterone
  • progesterone receptor B
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A
  • DNMT1 protein, human