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Molecular Signaling in Decidualization

蜕膜化中的分子信号传导

基本信息

批准号：
7905721
负责人：
SANJOY K. DAS
金额：
$ 52.49万
依托单位：
CINCINNATI CHILDRENS HOSP MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-15 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7905721
关键词：
Address Adenoviruses Anterior Basic Science Biological Models Cell Adhesion Molecules Cell Cycle Cell Differentiation process Cell Proliferation Collaborations Complement Complex Cyclins DTR gene Decidua Decidual Cell Decidual Cell Reactions Decidualization failure Deciduoma Development Developmental Process EGF gene Embryo Embryonic Development Ensure Epithelium Equilibrium Event Female Figs - dietary G1 Phase Goals Growth Growth Factor Homeobox Homeodomain Proteins Implant Incidence Infertility Knockout Mice Lead Molecular Molecular Genetics Multigene Family Mus Mutant Strains Mice Nutritional Support Phase Physiological Placentation Play Polyploidy Pregnancy Pregnancy Outcome Pregnancy loss Process Progesterone Reaction Research Research Design Role Scheme Signal Transduction Signaling Molecule Site Staging Stromal Cells Technology Time Uterus Vagina Wild Type Mouse Women&apos s Health blastocyst cyclin D3 cyclin G cyclin G1 cytokine failure Implantation implantation in vitro Model in vivo lipid mediator member morphogens natural Blastocyst Implantation overexpression response steroid hormone success transcription factor

项目摘要

Uterine stromal cell decidualization is integral to successful embryo implantation which is gateway to pregnancy establishment. This process is characterized by stromal cell proliferation and differentiation into decidual cells with polyploidy. Although various signaling molecules including cyclin D3 (a cell cycle regulator), HB-EGF (a heparinbinding EGF-like growth factor) and Hoxa-10 (a homeotic protein) are implicated in decidualization, the precise mechanisms by which these factors regulate this process and whether they are critical to decidualization are not known, except the essential role of Hoxa-10 in this process. We hypothesize that the success of decidualization is dependent on a balance between positive and negative regulators, directing proliferation and differentiation essential to this process; a tipping of this balance will lead to defective decidualization. We propose that Hoxa-10 and HB-EGF signaling converge to a common downstream cell cycle regulatory circuitry consisting of a positive cell cycle regulator cyclin D3 and negative cell cycle regulator cyclin G1 to appropriately balance proliferation and differentiation for achieving full complement of decidualization.

子宫间质细胞蜕膜化是胚胎着床成功的关键，也是妊娠成功的关键。该过程的特征在于基质细胞增殖并分化为具有多倍性的蜕膜细胞。尽管包括细胞周期蛋白D3（一种细胞周期调节因子）、HB-EGF（一种肝素结合EGF样生长因子）和Hoxa-10（一种同源异型蛋白）在内的各种信号分子都与蜕膜化有关，但这些因子调节这一过程的精确机制以及它们是否对蜕膜化至关重要尚不清楚，除了Hoxa-10在这一过程中的重要作用。我们假设，蜕膜化的成功是依赖于积极和消极的监管机构之间的平衡，指导增殖和分化至关重要的这一过程，这种平衡的倾斜将导致有缺陷的蜕膜化。我们建议，Hoxa-10和HB-EGF信号收敛到一个共同的下游细胞周期调节电路，包括一个积极的细胞周期调节细胞周期蛋白D3和细胞周期调节细胞周期蛋白G1，以适当地平衡增殖和分化，实现完整的补充蜕膜化。