权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Biological Role of Endometrial Glands in Uterine Function

子宫内膜腺在子宫功能中的生物学作用

基本信息

批准号：
9095068
负责人：
THOMAS E SPENCER
金额：
$ 18.3万
依托单位：
UNIVERSITY OF MISSOURI-COLUMBIA
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-12-06 至 2016-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9095068
关键词：
Affect Assisted Reproductive Technology Biochemical Biological Biological Markers Biology Clinical Collaborations Competence Complication Conceptions Conceptus Decidual Cell Decidual Cell Reactions Defect Diagnosis Embryo Embryo Transfer Endometrial Endometrial Stromal Cell Endometrium Ensure Epithelial Epithelial Cells Epithelium Female Fertility Fertilization in Vitro Foundations Future Gene Expression Profile Genes Genetic Models Gland Goals Growth Health Human Infertility Knowledge Lead Medicine Methods Molecular Mus Mutant Strains Mice Natural Killer Cells Outcome Physiological Pregnancy Pregnancy Outcome Pregnancy loss Preparation Prevention Procedures Process Publishing Reproductive Biology Research Rodent Role Stromal Cells Systems Biology Testing Uterine Gland Uterus Vascular remodeling Woman Work base blastocyst functional genomics implantation innovation interest mouse model mutant natural Blastocyst Implantation novel success uterine receptivity

项目摘要

DESCRIPTION (provided by applicant): Infertility and subfertility are pervasive problems in humans, and pregnancy loss is the most common complication of human gestation, with losses occurring most frequently in the first two weeks of gestation. Our long-range goal is to discover and understand the cellular and molecular mechanisms regulating uterine competency for pregnancy with a specific focus on uterine functions for blastocyst implantation in order to provide fundamental information useful for diagnosis, prevention and treatment of fertility problems. The receptive endometrium represents a temporary, but unique physiological state of the uterus when blastocyst growth and implantation is possible. Inadequate endometrial function, receptivity and decidualization negatively affect blastocyst implantation leading to pregnancy loss. Our central hypothesis is that endometrial glands and their secretions regulate endometrial receptivity, endometrial decidualization and blastocyst implantation. The goal of this proposal is to begin testing that hypothesis using a mouse model that lacks endometrial glands (conditional Foxa2 mutant). Specific aims are to: (1) determine the impact of endometrial glands and their secretions on endometrial receptivity and stromal decidualization; and (2) interrogate the endometrial epithelial transcriptome and secretome of early pregnancy. The systems biology approach, utilizing functional genomics and discovery-based methods in combination with a mouse model lacking endometrial glands, is innovative and could lead to identification of novel biomarkers of endometrial receptivity and uterine competency for pregnancy. Successful completion of the proposed research will fill a substantial gap in our scientific knowledge and impact the fields of uterine and pregnancy biology.

描述（由申请人提供）：不孕和生育力低下是人类普遍存在的问题，妊娠丢失是人类妊娠最常见的并发症，最常发生在妊娠的前两周。我们的长期目标是发现和了解调节子宫妊娠能力的细胞和分子机制，特别关注子宫的胚泡着床功能，以便为诊断，预防和治疗生育问题提供有用的基础信息。接受性子宫内膜代表了一种暂时的，但独特的生理状态，当胚泡生长和植入是可能的。子宫内膜功能、容受性和蜕膜化不足对胚泡着床产生负面影响，导致妊娠丢失。我们的中心假设是子宫内膜腺体及其分泌物调节子宫内膜容受性、子宫内膜蜕膜化和胚泡着床。本提案的目标是开始使用缺乏子宫内膜腺体的小鼠模型（条件性Foxa 2突变体）来测试该假设。具体目标是：（1）确定子宫内膜腺体及其分泌物对子宫内膜容受性和间质蜕膜化的影响;和（2）询问早期妊娠的子宫内膜上皮转录组和分泌组。系统生物学方法，利用功能基因组学和基于发现的方法结合缺乏子宫内膜腺体的小鼠模型，是创新的，并可能导致识别子宫内膜容受性和子宫妊娠能力的新生物标志物。成功完成拟议的研究将填补我们科学知识的重大空白，并影响子宫和妊娠生物学领域。