MCM2 mediates progesterone-induced endometrial stromal cell proliferation and differentiation in mice

Endocrine. 2016 Aug;53(2):595-606. doi: 10.1007/s12020-016-0894-9. Epub 2016 Feb 24.

Abstract

Uterine decidualization characterized by stromal cell proliferation and differentiation is critical to the establishment of pregnancy in many species. Progesterone is a key factor in regulating endometrial cell decidualization, however, the molecular basis involved in mediating the effects of progesterone during decidualization remains largely unknown. We report here that the DNA replication licensing factor MCM2, one of the conserved set of six-related proteins (MCM complex: MCM2-7) essential for eukaryotic DNA replication, is dynamically expressed in both proliferative and differentiated stromal cells during mouse periimplantation uterus. Applying PR-knockout mouse model and pharmacological strategy, we further found that the expression of Mcm2 is induced by progesterone action in the mouse uterine stroma. Employing a primary cell culture system, we further demonstrated that siRNA-mediated silencing of MCM2 arrests the cell cycle at G1-S transition during stromal cell proliferation. Moreover, the downregulation of Mcm2 could also compromise stromal cell differentiation. Collectively, our studies uncovered the role of a unique DNA replication licensing molecule MCM2 in mediating Progesterone-induced stromal cell decidualization in mouse uterus.

Keywords: Decidualization; Mcm2; Progesterone; S-phase; Uterine stroma.

MeSH terms

  • Animals
  • Cell Cycle / drug effects
  • Cell Cycle / physiology
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Cell Proliferation / drug effects
  • Cell Proliferation / physiology*
  • Endometrium / cytology
  • Endometrium / drug effects*
  • Endometrium / metabolism
  • Female
  • Mice
  • Mice, Knockout
  • Minichromosome Maintenance Complex Component 2 / genetics
  • Minichromosome Maintenance Complex Component 2 / metabolism*
  • Progesterone / pharmacology*
  • Stromal Cells / cytology
  • Stromal Cells / drug effects*
  • Stromal Cells / metabolism

Substances

  • Mcm2 protein, mouse
  • Progesterone
  • Minichromosome Maintenance Complex Component 2