Physiological Functions of Female Reproductive Tract Secretions

项目总结 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。 我们实验室最近的研究表明，精囊和卵巢旁的分泌细胞是两种类型的 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 输卵管和输卵管在排卵、精子储存和受精方面起着至关重要的作用。有了丰富的基因工具 我们开发了快速和精确的基因操作能力，我们建议利用这一新颖的 果蝇系统阐明分泌细胞调控的保守分子机制 排卵和精子储存。特别是，我们将描述保守转录因子的作用。 (NR5A家族核受体Hr39，GATA家族转录因子Pannier和Serpent)在分泌细胞中 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 分泌细胞发挥它们的作用，并利用遗传筛选识别用于精子存储的新的分泌因子。 这项工作将对女性生殖的分泌细胞生理学有一个全面的了解。 一条小路。这些信号通路的保守性将使从这项研究中获得的知识 在其他昆虫物种以及哺乳动物和人类输卵管中进一步得到验证。因此，这项工作将 最终揭示缓解不孕症、开发新型避孕药的有前景的新药靶点 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.