Molecular signaling in uterine receptivity to implantation

子宫植入容受性的分子信号传导

基本信息

批准号：
8877242
负责人：
Sudhansu K Dey
金额：
$ 31.7万
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：
2011
资助国家：
美国
起止时间：
2011-09-26 至 2016-09-10
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8877242
关键词：
Address Adherence Adhesions Animal Model Birth Blastocyst Transfer Cell Polarity Clinical Collaborations Complex Conceptions Contraceptive Agents Craniofacial Abnormalities Cytoskeleton Defect Development E-Cadherin Endometrium Epithelial Epithelial Cells Epithelium Estrogens Ethics Event Family Family member Female Female infertility Fertility Figs - dietary Food Gene Deletion Genes Goals Hair follicle structure Homeobox Homeobox Genes Human Implant Injection of therapeutic agent Letters Liquid substance Mammals Mesenchymal Modeling Molecular Mus Muscle Pattern Phase Play Powder dose form Pregnancy Pregnancy Rate Pregnancy loss Readiness Refractory Relative (related person)Reproduction Role Scientist Seizures Signal Pathway Signal Transduction Spontaneous abortion Testing Time Tooth structure Unwanted pregnancy Uterus Wild Type Mouse Woman base blastocyst clinically relevant craniofacial failure Implantation implantation improved mouse model natural Blastocyst Implantation novel novel strategies placental mammal psychologic research study success transcription factor uterine receptivity

项目摘要

DESCRIPTION (provided by applicant): Human reproduction is complex and not very efficient. More than 30% of conceptions result in spontaneous abortion with most losses occurring around the time of implantation due to an inadequate uterine milieu. Unwanted pregnancy loss is a major psychological, economical and clinical problem. One prerequisite for implantation in placental mammals is an effective two-way interaction between an implantation- competent blastocyst and the receptive uterus. The blastocyst will implant only when this molecular dialogue is established. The underlying mechanism by which a uterus transits from the pre-receptive to the receptive to the non-receptive phase remains unknown. We hypothesize that two highly conserved genes (Msx1 and Msx2) of the muscle segment homeobox (Msh) family have key roles in uterine receptivity and non-receptivity to implantation. In the proposed study, we will test the hypothesis that these morphogenetic genes, critical for epithelial-mesenchymal interactions during development, also play crucial roles in implantation by altering the epithelial cell polarity and integrity via a non- canonical Wnt signaling involving E-cadherin-2-catenin complex formation. To test our hypothesis, we will pursue two specific aims in mice. The first specific aim will test the hypothesis that while Msx1 is a major critical factor in implantation, Msx2 has a compensatory role if Msx1 is missing. The second specific aim will test the hypothesis that Msx1 and/or Msx2 direct implantation by influencing the epithelial cell polarity and integrity. The overall goal of this proposal is to better understand the mechanisms that direct uterine receptivity and non-receptivity with the aim of improving female fertility. We will use conditionally gene-deleted mouse models to address the molecular basis of these events, since these models provide mechanistic information relevant to female fertility which cannot be pursued in humans due to ethical restrictions. However, we will collaborate with clinician scientists to determine clinical correlates of our findings in mice.