Early growth response 1 transcriptionally primes the human endometrial stromal cell for decidualization

J Steroid Biochem Mol Biol. 2019 May;189:283-290. doi: 10.1016/j.jsbmb.2019.01.021. Epub 2019 Jan 31.

Abstract

Mouse studies support a role for endometrial early growth response 1 (EGR1) in uterine receptivity and decidualization, which are processes controlled by estrogen and progesterone. However, the importance of this transcription factor in similar cellular processes in human is unclear. Analysis of clinical samples indicate that endometrial EGR1 levels are decreased in the endometrium of women with recurrent implantation failure, suggesting that tight control of EGR1 levels are necessary for normal endometrial function. Therefore, we used siRNA-mediated knockdown of EGR1 expression in cultured human endometrial stromal cells (hESCs) to assess the functional role of EGR1 in hESC decidualization. Protein expression studies revealed that EGR1 is highly expressed in pre-decidual hESCs. However, EGR1 protein levels rapidly decrease following administration of an established deciduogenic hormone stimulus containing estradiol, medroxyprogesterone acetate, and cyclic adenosine monophosphate. Intriguingly, EGR1 knockdown in pre-decidual hESCs blocks the ability of these cells to decidualize later, indicating that EGR1 is required to transcriptionally program pre-decidual hESCs for decidualization. Support for this proposal comes from the analysis of transcriptome and cistrome datasets, which shows that EGR1 target genes are primarily involved in transcriptional regulation, cell signaling, and proliferation. Collectively, our studies provide translational support for an evolutionary conserved role for human endometrial stromal EGR1 in the early events of pregnancy establishment.

Keywords: ChIP-sequencing; Decidualization; Early growth response 1; Human endometrial stromal cells; Pregnancy; RNA-sequencing.

Publication types

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

MeSH terms

  • Animals
  • Cells, Cultured
  • Decidua / cytology*
  • Decidua / metabolism
  • Early Growth Response Protein 1 / genetics
  • Early Growth Response Protein 1 / metabolism*
  • Embryo Implantation
  • Endometrium / cytology*
  • Endometrium / metabolism
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Mice
  • Pregnancy
  • Stromal Cells / cytology*
  • Stromal Cells / metabolism
  • Transcriptional Activation

Substances

  • EGR1 protein, human
  • Early Growth Response Protein 1