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ANALYSIS OF REPRODUCTIVE FUNCTION USING TRANSGENIC MICE

使用转基因小鼠的生殖功能分析

基本信息

批准号：
7935154
负责人：
MARTIN M. MATZUK
金额：
$ 13.6万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2011-09-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7935154
关键词：
Address Antral Binding Binding Sites Cell Proliferation Cell Surface Receptors Cell physiology Cells Competence Complex Contraceptive Agents Development Dinoprostone Doctor of Medicine Doctor of Philosophy Female Fertility Fertilization Figs - dietary Follicle Stimulating Hormone Funding Future Gene Chips Gene Expression Genes Genetic Growth Growth Differentiation Factor 9 Growth Factor Human In Vitro Infertility Knock-out Knockout Mice LH Receptors Lead Ligands Luteinization Luteinizing Hormone Meiosis Messenger RNA Mus Oocytes Ovarian Ovarian Follicle Ovary Ovulation PTX3 protein Pathway interactions Pattern Peptides Play Primordial Follicle Process Proteins Protocols documentation Publishing Reagent Recombinant Proteins Recombinants Regulation Reporter Research Role Signal Transduction Somatic Cell Staging Steroids Transforming Growth Factors Transgenic Mice base cell growth folliculogenesis granulosa cell in vivo insight member mouse model novel oocyte maturation prevent programs receptor binding reproductive development reproductive function research study spatiotemporal theca cell

项目摘要

Reproductive development and function are complex processes requiring both extragonadal factors (e.g., FSH and LH) and intragonadal factors (e.g., steroids and peptide growth factors). Female fertility depends on the regulated allocation, growth, and maturation of oocytes, which must be coordinated with granulosa and theca cell proliferation and differentiation within the ovarian follicular unit. During this process, there are several transitions as follows: 1) Recruitment of quiescent primordial follicles to primary (one layer) follicles by an unknown mechanism; 2) Growth of the granulosa cells of the primary follicle to form two-layered and multi-layered secondary follicles; 3) Formation of antral follicles and further growth of the cells, a process which requires FSH; and 4) Transition of the antral follicle to a preovulatory follicle, in which mural granulosa cells and cumulus granulosa cells take on unique functions, a process induced by LH. Our currently funded competitive renewal (1996-present) hypothesized that the transforming growth factor p superfamily member, growth differentiation factor-9 (GDF-9), is a key oocyte-secreted factor required for transitions 2 and 4. GDF-9 mRNA and protein are specifically expressed within the oocyte beginning at the type 3a primary follicle stage and expressed through ovulation. Using GDF-9 knockout mice and recombinant mouse GDF-9, we have confirmed the above hypothesis. GDF-9 knockout mice are infertile due to a block in folliculogenesis at the primary follicle stage, and recombinant GDF-9 can substitute for the oocyte to regulate genes which are spatiotemporally expressed in the preovulatory ovarian follicle. Thus, GDF-9 is the first oocyte-secreted growth factor identified which plays multifunctional roles in the regulation of ovarian somatic cell function and gene expression. The studies described in this competitive renewal proposal will continue to use these key reagents (i.e., the GDF-9 knockout mice and recombinant GDF-9) and generate additional transgenic mouse models and reagents to further define the functions of GDF-9 and other essential regulators in granulosa cell and theca cell growth and differentiation.

生殖发育和功能是一个复杂的过程，需要睾丸外因素(例如，