Exploring sperm function

在射精时，精子不能受精。它们首先必须经历获能，这被广泛定义为使精子有能力受精的修饰。获能的一个标志是精子能够进行顶体反应，这是一种钙依赖的分泌事件，对卵子的细胞外基质透明带做出反应。精子是一种高度分割的非转录细胞，它是如何经历复杂的获能和顶体反应的尚不清楚。利用猪的模型，我们先前证明了获能与酪氨酸磷酸蛋白“p32”的出现有关。早期的蛋白质组学揭示，p32实际上是一个&gt；9酪氨酸磷酸蛋白的复合体，而在获能过程中出现的主要酪氨酸磷酸蛋白是Sp32。这种蛋白最初被认为是参与顶体成熟的顶体蛋白，然而，Sp32本身具有带状结合的亲和力，并被鉴定为癌症-睾丸抗原。我们的长期目标是在比较生物学的背景下，在基因和蛋白质水平上建立一个完整的精子功能模型，包括获能和顶体反应。我们的短期目标是鉴定、定位和鉴定p32复杂成分，鉴定Sp32，并鉴定介导获能和顶体反应的途径。这个项目将阐明翻译后蛋白质修饰如何导致精子能力，以及获能和顶体反应是如何调节的。这种受使用启发的基础研究有助于解决不育症的原因，制定合理的避孕措施，改进辅助生殖技术，并解释对男性生殖的毒理学影响。在人类和兽医、动物农业、病虫害防治以及保护濒危物种方面，生育控制是必要的。

At ejaculation, sperm cannot fertilise. They must first undergo capacitation, which is broadly defined as the modifications that render sperm competent to fertilise. A hallmark of capacitation is the ability of the sperm to undergo the acrosome reaction, a calcium-dependent, secretory event, in response to the egg's extracellular matrix, the zona pellucida. Just how the sperm, a highly compartmentalised and non-transcriptional cell, undergoes the complexities of capacitation and the acrosome reaction remains unclear. Using the porcine model, we previously showed that capacitation is associated with the appearance of "p32", a tyrosine phosphoprotein. Early proteomics revealed that p32 is actually a complex of >9 tyrosine phosphoproteins and that the principle tyrosine phosphoprotein appearing during capacitation to be Sp32. This protein was first known as an acrosomal protein involved in acrosin maturation, however, Sp32 itself has zona-binding affinity and has been identified as a cancer-testis antigen. Our long term objective is to establish an integrated model of sperm function at the gene and protein level including capacitation and the acrosome reaction in a context of comparative biology. Our short term objectives are to identify, localise and characterise p32 complex components, to characterise Sp32 and to identify the pathways mediating capacitation and the acrosome reaction. This program will clarify how post-translational protein modifications lead to sperm competence and how capacitation and the acrosome reaction are regulated. Such use-inspired basic research is instrumental to resolve causes of infertility, formulate rational contraception, improve assisted reproductive techniques, and interpret toxicological effects on male reproduction. Fertility control is necessary in human and veterinary medicine, animal agriculture, pest control, and to conserve endangered species.