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The Role and Branching Dynamics of Sympathetic Nerves in Ovarian Folliculogenesis

交感神经在卵巢卵泡发生中的作用和分支动态

基本信息

批准号：
10607058
负责人：
Eliza Ann Gaylord
金额：
$ 4.31万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-03-01 至 2026-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10607058
关键词：
3-Dimensional Ablation Adrenergic Agents Adult Affect Age Autocrine Communication Axon Biology Birth Data Data Set Delayed Puberty Destinations Development Disease Etiology Fellowship Female Fertility Genetic Glean Goals Gonadotropin Hormone Releasing Hormone Gonadotropins Graafian Follicles Growing Follicle Growth Image Infertility Knowledge Life Ligands Mammals Maps Measures Mediating Mentorship Microscopy Modeling Morphology Mus Neonatal Nerve Nerve Endings Nerve Fibers Neurons Oocytes Organ Organogenesis Ovarian Ovarian Diseases Ovary Ovulation Paracrine Communication Pathogenesis Pattern Peripheral Peripheral Nerves Polycystic Ovary Syndrome Presynaptic Terminals Primordial Follicle Process Production Puberty Regulation Reproductive Biology Research Role Signal Transduction Somatic Cell Source Testing Three-Dimensional Imaging Training Transgenic Mice United States WNT Signaling Pathway WNT5A gene Woman Work autocrine cell type folliculogenesis in vivo innovation insight mouse genetics mouse model nerve supply novel oocyte maturation ovarian reserve paracrine pharmacologic protein expression receptor reproductive spatiotemporal

项目摘要

PROJECT SUMMARY/ABSTRACT Although infertility affects 10% of women between the ages of 15 and 44 in the United States, fundamental gaps in knowledge surround ovary development. Ovarian folliculogenesis, defined as the production of mature and competent oocytes for ovulation, is a highly organized process that is critical for fertility. In mammals, the ‘ovarian reserve’ is comprised of single immature oocytes surrounded by a layer of somatic cells. This unit, known as a primordial follicle, remains non-growing until it activates and transitions through morphologically distinct stages of growth to support oocyte maturation. Follicle maturation occurs twice in mammalian life during separate waves of growth: first, around birth and second, at the onset of puberty. Distinct from the 2nd wave, which is initiated by release of gonadotropin hormone at puberty, the mechanisms underlying how 1st wave follicles are chosen to mature during this gonadotropin-independent wave remain elusive. As evidence indicates that sympathetic innervation may be involved in 1st wave follicle maturation, I propose to define the role and branching dynamics of sympathetic nerves (SNs) in the 1st wave of folliculogenesis. The overall hypothesis is that SNs innervate growing follicles via both autocrine and paracrine signaling and function to prime 1st wave follicles for gonadotropin-control. Elucidating how SNs influence female reproductive maturation and the mechanisms critical for establishing SN networks during the 1st wave of folliculogenesis will glean critical insights into the basic biology of this essential process and provide a platform for understanding ovarian disease pathogenesis. Leveraging innovative mouse genetics, whole organ clearing, 3D imaging, and quantitative analysis approaches, this proposal will: first, generate a 3D spatiotemporal map of SNs during 1st wave follicle maturation in the neonatal ovary; second, investigate the function of SNs in the 1st wave of follicle maturation; and third, interrogate the role of non-canonical Wnt-Ror1/2 signaling in the branching dynamics of SNs during the 1st wave of folliculogenesis. Sponsor Dr. Laird and co-sponsor Dr. Knox have complementary expertise in the fields of reproductive biology, genetic mouse models, 3D whole organ imaging and analysis, organogenesis, and peripheral nerve biology. Their collective expertise alongside the F31 Fellowship support assures the training and mentorship necessary to complete the proposed research.

项目总结/文摘