Functional Analysis of SMAD Signaling in Oocytes

卵母细胞 SMAD 信号传导的功能分析

基本信息

批准号：
8049865
负责人：
FRANCISCO J DIAZ
金额：
$ 7.37万
依托单位：
PENNSYLVANIA STATE UNIVERSITY, THE
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：
2011-02-01 至 2013-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8049865
关键词：
Activins Affect Age Age-Months Animals Antral BMP15 gene BMP2 gene BMP4 BMP6 gene Binding Biological Assay Breeding Cell Communication Cell Nucleus Cells Coculture Techniques Control Animal Defect Development Failure Female Fertility GDF9 gene Gene Expression Genes Growth Human Chorionic Gonadotropin Infertility Knowledge Ligands MADH2 gene MADH4 gene Mammals Measures Mediating Mediator of activation protein Menstrual cycle Messenger RNA Mus Mutant Strains Mice Nodal Nuclear Oocytes Oogenesis Ovarian Ovary Ovulation Pathway interactions Phosphorylation Premature Ovarian Failure Process Production Protein Family Proteins Reproduction Research Research Activity Signal Transduction Staining method Stains TGFB1 gene Testing Transcript Transforming Growth Factor beta Transforming Growth Factor beta Receptors base design granulosa cell improved inhibin insight male member mutant novel potency testing pup receptor research study therapy development transcription factor

项目摘要

DESCRIPTION (provided by applicant): The importance of oocyte-granulosa cell communication throughout oogenesis is well accepted. Members of the TGF-beta superfamily are important mediators of oocyte-granulosa cell communication, but the direct effect of these ligands on the oocyte is unclear. TGF-beta ligands activate SMAD proteins in target cells through phosphorylation. Activated SMADs (SMAD2/3 and 1/5/9) bind SMAD4 and translocate to the nucleus where they regulate nuclear functions. Based on preliminary analysis of mutant animals were the Smad4 gene is non-functional in oocytes, the present project tests the hypotheses that (1) Smad4 deletion in oocytes causes increased follicular development and (2) Smad4 mutant oocytes are more bioactive than control oocytes. Together, results from these two aims will provide valuable insight into mechanisms that affect oocyte development and may allow for development of interventions to improve oocyte quality and ovarian function. PUBLIC HEALTH RELEVANCE: The proposed research activities will increase our understanding of ovarian function, follicular and oocyte development. This knowledge will improve our ability to treat problems associated with defects in female reproduction, including infertility, premature ovarian failure and irregular menstrual cycles.

描述（由申请人提供）：整个卵子发生的卵母细胞粒细胞通信的重要性已被广泛接受。 TGF-β超家族的成员是卵母细胞粒细胞通信的重要介质，但是这些配体对卵母细胞的直接作用尚不清楚。 TGF-β配体通过磷酸化激活靶细胞中的Smad蛋白。活化的SMADS（SMAD2/3和1/5/9）结合Smad4并转移到调节核功能的细胞核上。基于对突变动物的初步分析，SMAD4基因在卵母细胞中是非功能性的，目前的项目检验了（（1）卵母细胞中SMAD4缺失会导致卵泡发育增加，并且（2）SMAD4突变体卵母细胞比对照卵母细胞更具生物活性。总之，这两个目标的结果将提供对影响卵母细胞发展的机制的宝贵见解，并可以开发干预措施以改善卵母细胞质量和卵巢功能。公共卫生相关性：拟议的研究活动将增加我们对卵巢功能，卵泡和卵母细胞发展的理解。这些知识将提高我们治疗与女性繁殖缺陷相关的问题的能力，包括不育症，早产卵巢衰竭和不规则的月经周期。