Control of regional decidualization in implantation: Role of FoxM1 downstream of Hoxa10 and cyclin D3.
Appropriate regulation of regional uterine stromal cell decidualization in implantation, at the mesometrial triangle and secondary decidual zone (SDZ) locations, is critical for successful pregnancy, although the regulatory mechanisms remain poorly understood. In this regard, the available animal models that would specifically allow mechanistic analysis of site-specific decidualization are strikingly limited. Our study found that heightened expression of FoxM1, a Forkhead box transcription factor, is regulated during decidualization, and its conditional deletion in mice reveals failure of implantation with regional decidualization defects such as a much smaller mesometrial decidua with enlarged SDZ. Analysis of cell cycle progression during decidualization both in vivo and in vitro demonstrates that the loss of FoxM1 elicits diploid cell deficiency with enhanced arrests prior to mitosis and concomitant upregulation of polyploidy. We further showed that Hoxa10 and cyclin D3, two decidual markers, control transcriptional regulation and intra-nuclear protein translocation of FoxM1 in polyploid cells, respectively. Overall, we suggest that proper regional decidualization and polyploidy development requires FoxM1 signaling downstream of Hoxa10 and cyclin D3.
Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.|Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Fei
F
Gao
Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.|Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Fenghua
F
Bian
Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.|Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.|College of Life Science, Northeast Agricultural University, Harbin, China.
Xinghong
X
Ma
Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.|Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Vladimir V
VV
Kalinichenko
Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.|Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Sanjoy K
SK
Das
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation; D049109:Cell Proliferation; D056743:Cyclin D3 / Q000378:metabolism*; D003656:Decidua / Q000473:pathology / Q000502:physiology*; D010064:Embryo Implantation / Q000502:physiology*; D005260:Female; D005298:Fertility / Q000235:genetics; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D005786:Gene Expression Regulation; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D008938:Mitosis / Q000235:genetics; D011123:Polyploidy; D011247:Pregnancy; D021381:Protein Transport; D015398:Signal Transduction; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D014158:Transcription, Genetic
D056743:Cyclin D3; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; C491524:Foxm1 protein, mouse; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; C092119:Hoxa10 protein, mouse