"Physical and Chemical Cues that Guide Sperm Migration"

“引导精子迁移的物理和化学线索”

• 批准号: 8437156
• 负责人: Susan Stevens Suarez
• 金额: $ 29.21万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8437156
• 关键词: Affect; Annexins; Artificial Insemination; Assisted Reproductive Technology; Binding; Biochemical; Biological Models; Cattle; Cervix Uteri; Chemicals; Contraceptive Agents; Contraceptive methods; Couples; Cues; Development; Diagnosis; Dose; Drops; Epithelium; Farming environment; Female; Fertility; Fertilization; Fetus; Goals; Health; Human; Immigration; Industry; Infertility; Insemination; Intracytoplasmic Sperm Injections; Investigation; Liquid substance; Low Birth Weight Infant; Mammalian Oviducts; Mastigophora; Mediating; Medicine; Methods; Microfluidics; Modeling; Modification; Movement; Outcome; Parasites; Partner in relationship; Physical environment; Play; Premature Birth; Procedures; Process; Proteins; Reproductive Health; Reproductive Technology; Risk; Role; Seminal fluid; Sexual Development; Sexually Transmitted Diseases; Sperm Count Procedure; Stress; Testing; Trichomonas Infections; Trichomonas vaginalis; Tritrichomonas foetus; Unwanted pregnancy; Vagina; Work; cell motility; egg; fluid flow; improved; male; migration; pathogen; preference; pressure; prevent; reproductive; sperm cell; sperm protein; success; time use; viscoelasticity

DESCRIPTION (provided by applicant): The long-term goal of our work is to understand the interactions of sperm with the female reproductive tract that are required for fertilization. Infertility affects about 7% of married couples in the US and the success rate of artificial insemination in the cattle industry has been dropping over the past several years. Sexually transmitted diseases (STDs) such as trichomoniasis are a major problem for both humans and cattle. Lastly, safer forms of contraception are needed for humans. Understanding the processes of sperm and pathogen migration through the female reproductive tract could enable the development of new methods for diagnosing and treating infertility, protecting against STDs, and preventing unwanted pregnancies. We are proposing a unique two-pronged approach to identify biophysical and biochemical factors that promote sperm migration to the egg but also inhibit the rise of STD pathogens, particularly those causing trichomoniasis. For this project, the bovine model will not only provide useful information to the cattle industry but also to human medicine, because biophysical and biochemical aspects of the migration of bull sperm through the cervix, uterotubal junction, and oviduct are quite similar to those of humans. Aim 1 is to identify roles of physical factors that guide sperm migration in the cervix and uterotubal junction. To achieve this, we will carry out the following subaims. 1A. Develop a microfluidic model that mimics three parameters of the physical environments of the passages in the cervix and uterotubal junction: the microchannels in the walls of the main central channel, fluid flow, and fluid viscoelasticity. 1B. Test the hypothesis that microchannels in the walls of the cervix and uterotubal junction assist sperm in moving upstream in the presence of a flow. As part of the investigation, we will explore the roles of fluid viscoelasticity in facilitating sperm migration against the flow. 1C. Test the hypothesis that physical parameters facilitate the entry of sperm into the microchannels in preference to entry of pathogens, particularly Tritrichomonas foetus. Aim 2 is to elucidate how the molecules involved in binding sperm to oviductal epithelium regulate sperm migration up the oviduct. We will test the hypothesis that loss and modification of Binder of Sperm proteins (BSPs) play crucial roles in releasing sperm from the oviductal storage reservoir toward the upper oviduct. Binding of bull sperm to oviductal epithelium is mediated by 3 BSPs on sperm, which interact with 4 annexin proteins (ANXAs) on the oviductal epithelium. Binding is reduced by capacitation, so we propose to test its effects on BSPs and on release of sperm from oviductal epithelium, as well as the role that the interactions of BSPs with ANXAs could play in guiding sperm to the egg.

描述（由申请人提供）：我们工作的长期目标是了解精子与受精所需的女性生殖道的相互作用。不孕症影响着美国约7%的已婚夫妇，在过去几年中，养牛业人工授精的成功率一直在下降。性传播疾病（STD），如滴虫病是人类和牛的主要问题。最后，人类需要更安全的避孕方式。了解精子和病原体通过女性生殖道迁移的过程可以开发诊断和治疗不孕症，预防性病和预防意外怀孕的新方法。我们提出了一种独特的双管齐下的方法，以确定生物物理和生物化学因素，促进精子迁移到卵子，但也抑制性病病原体的上升，特别是那些引起滴虫病。对于该项目，牛模型不仅将为养牛业提供有用的信息，还将为人类医学提供有用的信息，因为公牛精子通过子宫颈、子宫输卵管连接处和输卵管的迁移的生物物理和生物化学方面与人类非常相似。目的1是确定物理因素的作用，引导精子在子宫颈和子宫输卵管交界处的迁移。为实现这一目标，我们将实现以下次级目标。1A.开发一个微流体模型，模拟子宫颈和子宫输卵管交界处通道的物理环境的三个参数：主中央通道壁中的微通道，流体流动和流体粘弹性。1B.验证子宫颈壁和子宫输卵管交界处的微通道有助于精子在存在流动的情况下向上游移动的假设。作为研究的一部分，我们将探讨流体粘弹性在促进精子逆流迁移中的作用。1C.检验以下假设：物理参数有利于精子进入微通道，而不是病原体（特别是胎儿三毛滴虫）进入。目的二是阐明精子与输卵管上皮结合的分子如何调控精子沿输卵管向上迁移。我们将检验精子结合蛋白（BSPs）的缺失和修饰在将精子从输卵管储库释放到输卵管上部中起关键作用的假设。牛精子与输卵管上皮的结合是由精子上的3种BSP介导的，它们与输卵管上皮上的4种膜联蛋白（ANXA）相互作用。获能降低了结合，因此我们建议测试其对BSP和精子从输卵管上皮释放的影响，以及BSP与ANXA的相互作用在引导精子进入卵子中可能发挥的作用。