Physiological Functions of Female Reproductive Tract Secretions

项目摘要 输卵管分泌物是准备配子受精所必需的，整个过程都是保守的。 动物王国然而，输卵管生理学的分子机制在很大程度上是未知的。 本实验室最近的研究表明，受精囊和卵巢旁腺的分泌细胞， 果蝇雌性生殖道中的腺，在功能上与哺乳动物的分泌细胞同源， 输卵管，并发挥排卵，精子储存和受精的重要作用。有了丰富的基因工具 我们开发了快速和精确的遗传操作的能力，我们建议利用这种新的 果蝇系统，以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，我们将描述保守的转录因子的作用， （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点， 分泌细胞，以履行其职责，并确定新的分泌因子精子储存使用遗传筛选。 这项工作将提供一个全面的了解分泌细胞生理在女性生殖 道。这些信号通路的保守性将使从这项研究中获得的知识， 在其它昆虫物种以及哺乳动物和人类输卵管中进一步验证。因此，这项工作将 最终揭示了有希望的新药物靶点，用于缓解不孕症，用于新型避孕药， 发展，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

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.