Involvement of atypical transcription factor E2F8 in the polyploidization during mouse and human decidualization

Cell Cycle. 2015;14(12):1842-58. doi: 10.1080/15384101.2015.1033593.

Abstract

Polyploid decidual cells are specifically differentiated cells during mouse uterine decidualization. However, little is known about the regulatory mechanism and physiological significance of polyploidization in pregnancy. Here we report a novel role of E2F8 in the polyploidization of decidual cells in mice. E2F8 is highly expressed in decidual cells and regulated by progesterone through HB-EGF/EGFR/ERK/STAT3 signaling pathway. E2F8 transcriptionally suppresses CDK1, thus triggering the polyploidization of decidual cells. E2F8-mediated polyploidization is a response to stresses which are accompanied by decidualization. Interestingly, polyploidization is not detected during human decidualization with the down-regulation of E2F8, indicating differential expression of E2F8 may lead to the difference of decidual cell polyploidization between mice and humans.

Keywords: CDK1, cyclin-dependent kinase 1; CPT, Camptothecin; E2, estrogen; E2F8; MKC, megakaryocyte; P4, progesterone; PA, Purvalanol A; TGC, Trophoblast giant cell.; decidualization; polyploidization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CDC2 Protein Kinase / metabolism
  • Cell Line
  • Cyclin-Dependent Kinases / metabolism
  • DNA Damage
  • Decidua / physiology*
  • Female
  • Flow Cytometry
  • Hepatocytes / metabolism
  • Humans
  • Mice
  • Microscopy, Fluorescence
  • Ovary / metabolism
  • Polyploidy
  • Pregnancy
  • Pregnancy, Animal
  • Progesterone / metabolism
  • Repressor Proteins / physiology*
  • Signal Transduction
  • Superoxide Dismutase / metabolism
  • Uterus / metabolism

Substances

  • E2F8 protein, human
  • E2F8 protein, mouse
  • Repressor Proteins
  • Progesterone
  • Superoxide Dismutase
  • CDC2 Protein Kinase
  • CDK1 protein, human
  • Cyclin-Dependent Kinases