Retinoic acid signaling in decidualization

蜕膜化中的视黄酸信号传导

基本信息

  • 批准号:
    10280145
  • 负责人:
  • 金额:
    $ 33.86万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-08-09 至 2026-05-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY/ABSTRACT Human infertility is a global problem and failure of embryo implantation accounts for a significant percentage of pregnancy failure during both natural pregnancy and in vitro fertilization procedures. Implantation is an extremely complicated process requiring precisely controlled hormone signaling, growth factor signaling, and cell-cell interactions. Decidualization is a required step in the implantation process. It involves the rapid proliferation and differentiation of fibroblast-like endometrial stromal cells into epitheloid-like decidual cells. These cells become part of the decidual tissue that surrounds the implanting conceptus. Decidualization defects can directly lead to implantation failure. Moreover, early decidualization defects can cause other adverse pregnancy outcomes including abnormal placentation, restricted intrauterine fetal growth, and early parturition. Understanding decidualization is crucial for improving IVF success rates, developing novel contraceptives, and discovering new treatments for endometriosis. Despite its significance in reproduction, the genetic framework of decidualization had never been systematically studied until our recent development of a suitable high throughput screening tool, immortalized human endometrial stromal cells that carry the yellow fluorescent protein gene under the control of the progesterone-sensitive prolactin promoter (PRL-Y cells). We recently used PRL-Y cells to perform a whole genome siRNA functional screen to uncover novel regulatory genes for human decidualization. One major signaling pathway uncovered by the screen is the retinoic acid (RA) signaling pathway. Contrary to the current dogma that RA suppresses decidualization, we propose a paradigm-shifting hypothesis that RA signaling is absolutely required to initiate and promote decidualization, and is therefore required for female fertility. In this proposal, we will follow up on our exciting preliminary findings and study the function of RA signaling during decidualization through careful mapping of its downstream signaling pathways. In Aim I we will determine which RAR or combination of RARs is required during decidualization, and we will clarify the tissue-specific requirements for RA signaling during peri-implantation. In Aim II, we will identify RA downstream targets during decidualization in mouse and human. Finally in Aim III, we will investigate the interplay between RA and FGF signaling, and between RA and homeodomain proteins during decidualization. Successful completion of this project will dramatically increase our understanding of RA signaling during implantation/decidualization and will have an enduring impact on implantation biology and drug discovery.
项目总结/文摘

项目成果

期刊论文数量(0)
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Liang Ma其他文献

Liang Ma的其他文献

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{{ truncateString('Liang Ma', 18)}}的其他基金

Androgen and Wnt signaling in bladder cancer
膀胱癌中的雄激素和 Wnt 信号传导
  • 批准号:
    10727745
  • 财政年份:
    2023
  • 资助金额:
    $ 33.86万
  • 项目类别:
Retinoic acid signaling in decidualization
蜕膜化中的视黄酸信号传导
  • 批准号:
    10619637
  • 财政年份:
    2021
  • 资助金额:
    $ 33.86万
  • 项目类别:
GENITALIA OUTGROWTH AND HYPOSPADIAS
生殖器生长和尿道下裂
  • 批准号:
    9317645
  • 财政年份:
    2017
  • 资助金额:
    $ 33.86万
  • 项目类别:
GENOME-WIDE IDENTIFICATION OF GENES REQUIRED FOR DECIDUALIZATION
蜕化所需基因的全基因组鉴定
  • 批准号:
    9258455
  • 财政年份:
    2016
  • 资助金额:
    $ 33.86万
  • 项目类别:
AN IN VITRO SCREENING TOOL FOR DECIDUALIZATION
一种用于分化的体外筛选工具
  • 批准号:
    8969886
  • 财政年份:
    2015
  • 资助金额:
    $ 33.86万
  • 项目类别:
GENERATION OF AN INDUCIBLE SYSTEM IN THE UTERINE STROMA FOR IMPLANTATION STUDIES
用于植入研究的子宫间质中诱导系统的生成
  • 批准号:
    8358586
  • 财政年份:
    2012
  • 资助金额:
    $ 33.86万
  • 项目类别:
GENERATION OF AN INDUCIBLE SYSTEM IN THE UTERINE STROMA FOR IMPLANTATION STUDIES
用于植入研究的子宫间质中诱导系统的生成
  • 批准号:
    8522211
  • 财政年份:
    2012
  • 资助金额:
    $ 33.86万
  • 项目类别:
EXTERNAL GENITALIA DEVELOPMENT AND HYPOSPADIAS
外生殖器发育和尿道下裂
  • 批准号:
    7656161
  • 财政年份:
    2009
  • 资助金额:
    $ 33.86万
  • 项目类别:
Novel effectors of ERK signaling and their potential roles in the treatment of en
ERK 信号传导的新型效应物及其在治疗 en 中的潜在作用
  • 批准号:
    7727351
  • 财政年份:
    2009
  • 资助金额:
    $ 33.86万
  • 项目类别:
EXTERNAL GENITALIA DEVELOPMENT AND HYPOSPADIAS
外生殖器发育和尿道下裂
  • 批准号:
    8265869
  • 财政年份:
    2009
  • 资助金额:
    $ 33.86万
  • 项目类别:

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