FoxM1 influences embryo implantation and is regulated by 17 beta-estradiol and progesterone in mouse uteri and endometrium cells

Int J Clin Exp Pathol. 2014 Sep 15;7(10):6585-95. eCollection 2014.

Abstract

To be a successful implantation, endometrial receptivity should be established. Forkhead box M1 (FoxM1) is described as a major oncogenic transcription factor in tumor initiation, promotion, and progression. FoxM1 regulates the expression of lots of targeted genes important to cell differentiation, proliferation and apoptosis; cell-cycle progression; and tumor angiogenesis, migration, invasion, and metastasis. According to these functions, we believe that FoxM1 should also play an essential role in embryo implantation. To test our hypothesis, we observed the expression and distribution of FoxM1 during the early pregnancy of mouse. Then, we used Immunohistochemistry to examine the expression of FoxM1 induced by E2 and/or P4 in the ovariectomized mouse uterus and human endometrium cells. This study further investigated whether FoxM1 was an important factor in the implantation. Our results showed that FoxM1 expressed in the mouse uterus during early pregnancy (Day 1 to 5). The expression of FoxM1 gradually increased along pregnancy process; FoxM1 expression could be increased by E2. On the contrary, FoxM1 expression could be decreased by P4 and E2 plus P4. We also detected the proliferation of human endometrium cells. We found that E2 might promote cells proliferation, while P4 and E2 plus P4 inhibited cells proliferation; Inhibiting FoxM1 could interfere the embryo implantation of mouse. Amplification or inhibiting of FoxM1 in JAR cells can increase or decrease the adhesion rate to Rl95-2 and HEC-1A cells separately. Our data indicate that FoxM1 might play an important role during the process of mouse embryo implantation.

Keywords: E2; FoxM1; P4; implantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Embryo Implantation / drug effects*
  • Endometrium / metabolism*
  • Estradiol / pharmacology*
  • Female
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Gestational Age
  • Humans
  • Mice
  • Ovariectomy
  • Pregnancy
  • Progesterone / pharmacology*
  • RNA Interference
  • Signal Transduction / drug effects
  • Time Factors
  • Transfection
  • Uterus / drug effects*
  • Uterus / metabolism

Substances

  • FOXM1 protein, human
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors
  • Foxm1 protein, mouse
  • Progesterone
  • Estradiol