A murine uterine transcriptome, responsive to steroid receptor coactivator-2, reveals transcription factor 23 as essential for decidualization of human endometrial stromal cells

Biol Reprod. 2014 Apr 10;90(4):75. doi: 10.1095/biolreprod.114.117531. Print 2014 Apr.


Recent data from human and mouse studies strongly support an indispensable role for steroid receptor coactivator-2 (SRC-2)-a member of the p160/SRC family of coregulators-in progesterone-dependent endometrial stromal cell decidualization, an essential cellular transformation process that regulates invasion of the developing embryo into the maternal compartment. To identify the key progesterone-induced transcriptional changes that are dependent on SRC-2 and required for endometrial decidualization, we performed comparative genome-wide transcriptional profiling of endometrial tissue RNA from ovariectomized SRC-2(flox/flox) (SRC-2(f/f) [control]) and PR(cre/+)/SRC-2(flox/flox) (SRC-2(d/d) [SRC-2-depleted]) mice, acutely treated with vehicle or progesterone. Although data mining revealed that only a small subset of the total progesterone-dependent transcriptional changes is dependent on SRC-2 (∼13%), key genes previously reported to mediate progesterone-driven endometrial stromal cell decidualization are present within this subset. Along with providing a more detailed molecular portrait of the decidual transcriptional program governed by SRC-2, the degree of functional diversity of these progesterone mediators underscores the pleiotropic regulatory role of SRC-2 in this tissue. To showcase the utility of this powerful informational resource to uncover novel signaling paradigms, we stratified the total SRC-2-dependent subset of progesterone-induced transcriptional changes in terms of novel gene expression and identified transcription factor 23 (Tcf23), a basic-helix-loop-helix transcription factor, as a new progesterone-induced target gene that requires SRC-2 for full induction. Importantly, using primary human endometrial stromal cells in culture, we demonstrate that TCF23 function is essential for progesterone-dependent decidualization, providing crucial translational support for this transcription factor as a new decidual mediator of progesterone action.

Keywords: decidualization; endometrium; human; microarray; mouse; progesterone; steroid receptor coactivator-2; transcription factor 23.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Decidua / cytology*
  • Decidua / physiology
  • Female
  • Humans
  • Mice
  • Mice, Mutant Strains
  • Nuclear Receptor Coactivator 2 / genetics*
  • Nuclear Receptor Coactivator 2 / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Pregnancy
  • Progesterone / metabolism
  • RNA, Small Interfering / genetics
  • Stromal Cells / cytology*
  • Stromal Cells / physiology
  • Transcription, Genetic / physiology
  • Transcriptome / physiology
  • Uterus / cytology
  • Uterus / physiology


  • Basic Helix-Loop-Helix Transcription Factors
  • NCOA2 protein, human
  • Ncoa2 protein, mouse
  • Nuclear Receptor Coactivator 2
  • RNA, Small Interfering
  • TCF23 protein, human
  • Tcf23 protein, mouse
  • Progesterone