The Center for Reproductive Biological Research

生殖生物学研究中心

基本信息

  • 批准号:
    6963445
  • 负责人:
  • 金额:
    $ 18.23万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2005
  • 资助国家:
    美国
  • 起止时间:
    2005-07-25 至 2009-03-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Interactions between developing gametes and their neighboring somatic cells are essential for normal fertility. Studies over the last decade established that bidirectional communication between the oocyte and companion granulosa cells is essential for folliculogenesis and development of an egg competent to undergo fertilization and embryogenesis. The Matzuk laboratory and others delineated roles for oocyte-secreted factors such as growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) in the regulation of folliculogenesis in mammals. In the process, the Matzuk laboratory produced key reagents (i.e., recombinant mouse GDF9, monoclonal antibodies that detect mouse GDF9 by immunohistochemistry and Gdf9 and Gdf9/Bmp15 knockout mice that are infertile) that were useful for the above studies and helped to identify cumulus granulosa cell genes that are directly regulated by GDF9. Recent evidence supports the presence of GDF9 and BMP 15 mRNA and protein in the ovary of primates, and the downregulation of GDF9 mRNA in women with polycystic ovarian syndrome. However, little is known about the significance of GDF9 and BMP 15 in oocyte-somatic cell communication during follicular development in primates or in human diseases. An important role for GDF9 and/or BMP15 can be implied from the recent data of Dr. Matzuk and colleagues that levels of expression of GDF9-regulated cumulus cell genes correlate with subsequent embryo development during assisted reproductive protocols in infertile women. The following translational study was designed to: 1) develop important GDF9 and BMP 15 related reagents; and 2) begin investigations to unravel the functions of GDF9 and BMP15 in oocyte-granulosa cell interactions during preovulatory follicular development in primates. The Specific Aims of the proposed U54 collaborative research initiative are as follows: 1) Produce large amounts of purified recombinant human GDF9 and BMP15 and anti-GDF9 and anti-BMP 15 neutralizing antibodies for in vitro and in vivo studies; and 2) Use bioactive GDF9 and BMP15 and anti-human GDF9/BMP15 antibodies for comparative analysis of gene expression and functional assays in mouse, nonhuman primate, and human pre-ovulatory granulosa cells/cumulus cell-oocyte complex systems. The current collaboration between Drs. Martin M. Matzuk and Richard L. Stouffer should yield important and clinically relevant findings for understanding human ovarian function, fertility, and reproductive diseases.
描述(由申请人提供):发育中的配子及其邻近体细胞之间的相互作用对正常生育力至关重要。过去十年的研究表明,卵母细胞和伴侣颗粒细胞之间的双向通讯对于卵泡发生和卵子发育至关重要,卵子能够进行受精和胚胎发生。Matzuk实验室和其他人描述了卵母细胞分泌因子如生长分化因子9(GDF 9)和骨形态发生蛋白15(BMP 15)在哺乳动物卵泡发生调节中的作用。在这个过程中,Matzuk实验室生产了关键试剂(即,重组小鼠GDF 9、通过免疫组织化学检测小鼠GDF 9的单克隆抗体和不育的Gdf 9和Gdf 9/Bmp 15敲除小鼠),其可用于上述研究并有助于鉴定直接受GDF 9调节的卵丘颗粒细胞基因。最近的证据支持GDF 9和BMP 15 mRNA和蛋白在灵长类动物卵巢中的存在,以及GDF 9 mRNA在多囊卵巢综合征女性中的下调。然而,很少有人知道GDF 9和BMP 15在卵母细胞-体细胞通信在卵泡发育过程中在灵长类动物或人类疾病的意义。Matzuk博士及其同事的最新数据表明,GDF 9和/或BMP 15的重要作用在于,GDF 9调节的卵丘细胞基因的表达水平与不孕妇女辅助生殖方案期间随后的胚胎发育相关。以下翻译研究旨在:1)开发重要的GDF 9和BMP 15相关试剂;和2)开始研究,以阐明GDF 9和BMP 15在灵长类动物排卵前卵泡发育期间卵母细胞-颗粒细胞相互作用中的功能。U 54合作研究计划的具体目标如下:1)生产大量纯化的重组人GDF 9和BMP 15以及抗GDF 9和抗BMP 15中和抗体,用于体外和体内研究;和2)使用生物活性GDF 9和BMP 15以及抗人GDF 9/BMP 15抗体用于小鼠中基因表达和功能测定的比较分析,非人灵长类动物和人排卵前颗粒细胞/卵丘细胞-卵母细胞复合体系统。目前的合作博士马丁M。作者声明:Richard L. Stouffer应该产生重要的和临床相关的研究结果,了解人类卵巢功能,生育能力和生殖疾病。

项目成果

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BERT W O'MALLEY其他文献

BERT W O'MALLEY的其他文献

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{{ truncateString('BERT W O'MALLEY', 18)}}的其他基金

Project 3: Coactivator-dependent hepatic 12h clock coordinates metabolic and stress rhythms
项目 3:共激活剂依赖性肝脏 12 小时时钟协调代谢和应激节律
  • 批准号:
    10421284
  • 财政年份:
    2018
  • 资助金额:
    $ 18.23万
  • 项目类别:
Core A (Administrative/Bioinformatics/Statistics)
核心A(管理/生物信息学/统计学)
  • 批准号:
    10153757
  • 财政年份:
    2018
  • 资助金额:
    $ 18.23万
  • 项目类别:
Nuclear receptors and their Coactivators as Mediators of Systems Metabolism
核受体及其共激活剂作为系统代谢的调节剂
  • 批准号:
    10421277
  • 财政年份:
    2018
  • 资助金额:
    $ 18.23万
  • 项目类别:
Project 3: Coactivator-dependent hepatic 12h clock coordinates metabolic and stress rhythms
项目 3:共激活剂依赖性肝脏 12 小时时钟协调代谢和应激节律
  • 批准号:
    10153762
  • 财政年份:
    2018
  • 资助金额:
    $ 18.23万
  • 项目类别:
Nuclear receptors and their Coactivators as Mediators of Systems Metabolism
核受体及其共激活剂作为系统代谢的调节剂
  • 批准号:
    10153756
  • 财政年份:
    2018
  • 资助金额:
    $ 18.23万
  • 项目类别:
Core A (Administrative/Bioinformatics/Statistics)
核心A(管理/生物信息学/统计学)
  • 批准号:
    10421278
  • 财政年份:
    2018
  • 资助金额:
    $ 18.23万
  • 项目类别:
Nuclear receptors and their Coactivators as Mediators of Systems Metabolism
核受体及其共激活剂作为系统代谢的调节剂
  • 批准号:
    9975144
  • 财政年份:
    2018
  • 资助金额:
    $ 18.23万
  • 项目类别:
The ERbeta/SRC-1 isoform complex drives endometriosis progression
ERbeta/SRC-1亚型复合物驱动子宫内膜异位症进展
  • 批准号:
    8823016
  • 财政年份:
    2014
  • 资助金额:
    $ 18.23万
  • 项目类别:
The ERbeta/SRC-1 isoform complex drives endometriosis progression
ERbeta/SRC-1亚型复合物驱动子宫内膜异位症进展
  • 批准号:
    9258329
  • 财政年份:
    2014
  • 资助金额:
    $ 18.23万
  • 项目类别:
The ERbeta/SRC-1 isoform complex drives endometriosis progression
ERbeta/SRC-1亚型复合物驱动子宫内膜异位症进展
  • 批准号:
    8893195
  • 财政年份:
    2014
  • 资助金额:
    $ 18.23万
  • 项目类别:

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Ebola virus infection of the female reproductive system
埃博拉病毒感染女性生殖系统
  • 批准号:
    10396086
  • 财政年份:
    2021
  • 资助金额:
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  • 项目类别:
Ebola virus infection of the female reproductive system
埃博拉病毒感染女性生殖系统
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    $ 18.23万
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Penn Center for Multi-scale Molecular Mapping of the Female Reproductive System
宾夕法尼亚大学女性生殖系统多尺度分子图谱中心
  • 批准号:
    10413658
  • 财政年份:
    2020
  • 资助金额:
    $ 18.23万
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Penn Center for Multi-scale Molecular Mapping of the Female Reproductive System
宾夕法尼亚大学女性生殖系统多尺度分子图谱中心
  • 批准号:
    10117836
  • 财政年份:
    2020
  • 资助金额:
    $ 18.23万
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Penn Center for Multi-scale Molecular Mapping of the Female Reproductive System
宾夕法尼亚大学女性生殖系统多尺度分子图谱中心
  • 批准号:
    10269925
  • 财政年份:
    2020
  • 资助金额:
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Penn Center for Multi-scale Molecular Mapping of the Female Reproductive System
宾夕法尼亚大学女性生殖系统多尺度分子图谱中心
  • 批准号:
    10461161
  • 财政年份:
    2020
  • 资助金额:
    $ 18.23万
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Penn Center for Multi-scale Molecular Mapping of the Female Reproductive System
宾夕法尼亚大学女性生殖系统多尺度分子图谱中心
  • 批准号:
    10653357
  • 财政年份:
    2020
  • 资助金额:
    $ 18.23万
  • 项目类别:
Penn Center for Multi-scale Molecular Mapping of the Female Reproductive System
宾夕法尼亚大学女性生殖系统多尺度分子图谱中心
  • 批准号:
    10822203
  • 财政年份:
    2020
  • 资助金额:
    $ 18.23万
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Cell atlas of the human female reproductive system across the lifespan
人类女性生殖系统整个生命周期的细胞图谱
  • 批准号:
    MR/S036350/1
  • 财政年份:
    2018
  • 资助金额:
    $ 18.23万
  • 项目类别:
    Research Grant
Role of USP15 in pregnancy and female reproductive system
USP15 在妊娠和女性生殖系统中的作用
  • 批准号:
    17K17919
  • 财政年份:
    2017
  • 资助金额:
    $ 18.23万
  • 项目类别:
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