title: HB-EGF directs stromal cell polyploidy and decidualization via cyclin D3 during implantation.
abstract: Stromal cell polyploidy is a unique phenomenon that occurs during uterine decidualization following embryo implantation, although the developmental mechanism still remains elusive. The general consensus is that the aberrant expression and altered functional activity of cell cycle regulatory molecules at two particular checkpoints G1 to S and G2 to M in the cell cycle play an important role in the development of cellular polyploidy. Despite the compelling evidence of intrinsic cell cycle alteration, it has been implicated that the development of cellular polyploidy may be controlled by specific actions of extracellular growth regulators. Here we show a novel role for heparin-binding EGF-like growth factor (HB-EGF) in the developmental process of stromal cell polyploidy in mice. HB-EGF, which is one of the earliest known molecular mediators of implantation in mice and humans, promotes stromal cell polyploidy via upregulation of cyclin D3. Adenoviral delivery of antisense cyclin D3 attenuates cyclin D3 expression and abrogates HB-EGF-induced stromal cell polyploidy in vitro and in vivo. Collectively, the results demonstrate that the regulation of stromal cell polyploidy and decidualization induced by HB-EGF depend on cyclin D3 induction.
authors.affiliation: Department of Pediatrics, Division of Reproductive and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232-2678, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tan
authors.forename: Meiling
authors.initials: M
authors.lastname: Li
authors.forename: Sandra
authors.initials: S
authors.lastname: Cox
authors.forename: Marilyn K
authors.initials: MK
authors.lastname: Davis
authors.forename: Ossama
authors.initials: O
authors.lastname: Tawfik
authors.forename: Bibhash C
authors.initials: BC
authors.lastname: Paria
authors.forename: Sanjoy K
authors.initials: SK
authors.lastname: Das
mesh_terms: D000256:Adenoviridae; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology; D056743:Cyclin D3; D016213:Cyclins / Q000378:metabolism*; D017931:DNA Primers; D010064:Embryo Implantation / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D005822:Genetic Vectors; D066257:Heparin-binding EGF-like Growth Factor; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008954:Models, Biological; D011123:Polyploidy; D011233:Precipitin Tests; D017154:Stromal Cells / Q000502:physiology; D014599:Uterus / Q000166:cytology* / Q000502:physiology
chemical_list: C534696:CCND3 protein, human; C534697:Ccnd3 protein, mouse; D056743:Cyclin D3; D016213:Cyclins; D017931:DNA Primers; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D004815:Epidermal Growth Factor