Understanding the molecular basis for sperm function: the sperm connecting piece and sperm motility

了解精子功能的分子基础：精子连接件和精子活力

• 批准号: 105414-2013
• 负责人: vanderHoorn, Frans
• 金额: $ 2.62万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629163
• 关键词: Understanding; molecular; basis; sperm; function

Spermatozoa are motile cells that transfer the father's genetic information to the oocyte. To function, sperm morphology must be normal, and sperm must acquire motility. Often, animal (and human) male infertility is related to abnormal sperm morphology and function. One phenotype, commonly observed for non-functional sperm, is sperm head detachment caused by a "fragile" sperm connecting piece. For cattle industry, high bull fertility is important and of economic consequence. We have discovered and characterized a sperm protein, p12 conserved among animal species, encoded by ornithine decarboxylase antizyme 3, Oaz3 gene. p12 modulates protein phosphatase activity, an important regulator of sperm motility. In sperm tails p12 likely regulates sperm tail motility but it is also present in the connecting piece. A mouse model shows that lack of p12 causes a fragile connecting piece phenotype and abnormal tail motility. This phenotype closely resembles observations made in the bovine industry.We propose to investigate how p12 is involved in regulation of sperm tail motility and in the connecting piece. We will a) analyze to which proteins p12 binds in the connecting piece, b) analyze if p12 regulates phosphorylation of connecting piece proteins, c) the importance of the association of p12 with Mypt3 on phosphatase activity in the sperm tail and regulation of motility, and d) analyze p12 function in sperm tail motility using novel transgenic mouse models for p12 using specific p12 mutant proteins.Our experiments will address a common problem in the cattle industry, and will provide tools to equip industry using reproductive technologies to diagnose sperm and optimize procedures.

精子是将父亲的遗传信息转移到卵母细胞的活动细胞。为了发挥功能，精子形态必须正常，并且精子必须获得活力。通常，动物（和人类）男性不育症与精子形态和功能异常有关。无功能精子中常见的一种表型是由“脆弱”精子连接件引起的精子头部脱离。对于养牛业来说，高公牛繁殖力非常重要，并且具有经济意义。我们发现并鉴定了动物物种中保守的精子蛋白 p12，由鸟氨酸脱羧酶抗酶 3（Oaz3 基因）编码。 p12 调节蛋白磷酸酶活性，这是精子活力的重要调节因子。在精子尾部中，p12 可能调节精子尾部的活力，但它也存在于连接部分中。小鼠模型表明，缺乏 p12 会导致脆弱的连接片表型和异常的尾部运动。这种表型与养牛业中的观察结果非常相似。我们建议研究 p12 如何参与精子尾部运动和连接部分的调节。我们将 a) 分析 p12 在连接件中结合哪些蛋白质，b) 分析 p12 是否调节连接件蛋白的磷酸化，c) p12 与 Mypt3 的关联对精子尾部磷酸酶活性和运动调节的重要性，以及 d) 使用特定 p12 突变蛋白的 p12 新型转基因小鼠模型分析 p12 在精子尾部运动中的功能。 实验将解决养牛业的一个常见问题，并将为使用生殖技术诊断精子和优化程序的行业提供工具。