Importance of intracellular signaling in the regulation of sperm fertilizing competence

精子是高度分化的细胞，其唯一作用是使卵子受精，以产生新的个体。为了实现这一目标，精子由两个相连的不同部分组成：头部和鞭毛，前者包含父亲一半的基因内容，后者是将基因内容与卵子接触所需的活动器官。虽然在睾丸出口处结构完整，但精子细胞在附睾期获得了移动和与排卵相互作用的能力。然而，它们只是保持不动，直到射精，当它们与精囊和前列腺的分泌物混合时。这个过程被称为动力激活。一旦进入女性生殖道，精子就会与细胞和分泌物相互作用，并在一个称为获能的过程中变得完全受精，这与精子运动的过度激活有关，精子运动更活跃，加快细胞速度和强度，以促进精子通过卵子相关的衣物，如卵丘和透明带，透明带是一种相对较厚的细胞外基质，由发育中的卵母细胞产生。尽管影响不同细胞内信号转导途径的药物参与了调节环磷酸腺苷、钙离子、pH-和蛋白质酪氨酸磷酸化介导的事件，但对获能和精子/卵子相互作用过程的调控机制尚不完全清楚。我的研究计划致力于进一步研究精子受精能力获得过程中的精子细胞内生化事件，并更好地描述精子与卵子相互作用所涉及的介体，这将导致受精和遗传独特个体的早期发育。这项研究计划无疑将对濒危物种、依赖于成功繁殖的农业行业(乳制品、肉类)遇到的生育问题产生影响，并最终对生活方式和环境对男性生育能力有强烈影响的人类产生影响。

Spermatozoa are highly differentiated cells which only role is to fertilize the egg in order to produce a new individual. To achieve its goal, spermatozoa are made of two distinct compartments linked together: the head which contains half of the paternal genetic content, and the flagellum, which is the mobility organ required to bring the genetic content in contact with the egg. Although structurally complete at the exit of the testis, sperm cells acquire the ability to move and to interact with the ovulated egg during the epididymal transit. However, they but remain in immotile until ejaculation, when they are mixed with the secretions from the seminal vesicles and the prostate. This process is called motility activation. Once in the female reproductive tract, sperm interacts with cells and secretion, and become fully fertilization competent in a process called capacitation and is associated with the hyperactivation of sperm motility, which is more vigorous, increasing cell velocity and strength to facilitate sperm passage through egg associated vestments such as the cumulus, a highly viscous proteoglycan-rich fluid containing cumulus cells linked together, and the zona pellucida, a relatively thick extracellular matrix produced by the growing oocyte. The mechanisms regulating the processes of capacitation and sperm/egg interactions are not fully understood although agents affecting different intracellular signal transduction pathways regulating cyclic AMP-, Ca2+-, pH-, and protein tyrosine phosphorylation-mediated events are involved. My research program is devoted to further investigate sperm intracellular biochemical events during the acquisition of sperm fertilizing ability and to better characterize the mediators involved in the sperm interactions with the egg that will result in fertilization and early development of a genetically unique individual. This research program will undoubtedly have impact on fertility problems encountered in endangered species, in agricultural industries (dairy, meat) that depend on successful reproduction and, ultimately in humans where lifestyle and environment have strong impacts on male fertility.