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Physiological Functions of Female Reproductive Tract Secretions

女性生殖道分泌物的生理功能

基本信息

批准号：
10377436
负责人：
Jianjun Sun
金额：
$ 32.74万
依托单位：
UNIVERSITY OF CONNECTICUT STORRS
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2025-10-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10377436
关键词：
Ablation Animals Arrestins Attention Cell physiology Cells Collection Contraceptive Agents Contraceptive methods Culicidae Data Development Drosophila genus Ecdysone Embryonic Development Family Female Fertilization Future Genetic Genetic Models Genetic Screening Germ Cells Gland Graafian Follicles Health Human Infertility Insecta Investigation Knowledge Lead Malaria Malignant Neoplasms Malignant neoplasm of ovary Mammalian Oviducts Mediating Medicine Methods Modeling Molecular Morphology Nature Nuclear Family Nuclear Receptors Orthologous Gene Ovary Ovulation Ovum Pathway interactions Physiological Physiology Play Population Process Proteins Regulation Reporting Reproductive Physiology Research Resolution Role Rupture Scientific Inquiry Secretory Cell Serous Signal Pathway Signal Transduction Steroids System Testing Therapeutic Tube Uterus Work extracellular vesicles falls genetic manipulation improved in vivo insight mosquito reproduction new therapeutic target novel novel strategies reproductive tract sperm cell tool transcription factor vector vesicular release

项目摘要

Project summary Secretions from oviducts are essential for preparing gametes for fertilization, processes conserved throughout the animal kingdom. However, molecular mechanisms underlying oviduct physiology are largely unknown. Recent studies from our lab have shown that secretory cells of spermathecae and parovaria, two types of glands in Drosophila female reproductive tract, are functionally homologous to secretory cells in mammalian oviducts and play essential roles for ovulation, sperm storage, and fertilization. With the wealth of genetic tools we developed and capability of rapid and precise genetic manipulation, we propose to utilize this novel Drosophila system to elucidate the conserved molecular mechanisms underlying secretory cell-regulated ovulation and sperm storage. Particularly, we will characterize the role of conserved transcription factors (NR5A-family nuclear receptor Hr39, GATA-family transcription factors Pannier and Serpent) in secretory cells for sperm storage and ovulation. We will also identify the downstream targets of these transcription factors in secretory cells to fulfill their roles and identify novel secretory factors for sperm storage using genetic screens. This work will provide a comprehensive understanding of the secretory cell physiology in female reproductive tract. The conserved nature of these signaling pathways will allow the knowledge gained from this study to be further validated in other insect species as well as in mammalian and human oviducts. Therefore, this work will ultimately reveal promising new drug targets for the alleviation of infertility, for novel contraceptive development, and for controlling malaria-bearing mosquito population, all of which are highly relevant to human health.

项目概要输卵管的分泌物对于准备受精配子至关重要，整个过程始终保持不变动物王国。然而，输卵管生理学的分子机制在很大程度上尚不清楚。我们实验室最近的研究表明，受精囊和细卵巢的分泌细胞（两种类型）果蝇雌性生殖道中的腺体在功能上与哺乳动物的分泌细胞同源输卵管对排卵、精子储存和受精起着重要作用。凭借丰富的遗传工具我们开发了快速、精确的基因操作能力，我们建议利用这种新颖的果蝇系统阐明分泌细胞调节的保守分子机制排卵和精子储存。特别是，我们将描述保守转录因子的作用分泌细胞中的（NR5A 家族核受体 Hr39、GATA 家族转录因子 Pannier 和 Serpent）用于精子储存和排卵。我们还将确定这些转录因子的下游靶标分泌细胞发挥其作用，并使用遗传筛选识别用于精子储存的新分泌因子。这项工作将提供对女性生殖分泌细胞生理学的全面了解道。这些信号通路的保守性将使从本研究中获得的知识能够在其他昆虫物种以及哺乳动物和人类输卵管中得到进一步验证。因此，这项工作将最终揭示有希望的新药物靶点，用于缓解不孕症和新型避孕药开发以及控制携带疟疾的蚊子种群，所有这些都与人类高度相关健康。