Intracellular signalling events leading to sperm fertilization 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，当它们与精囊和前列腺的分泌物混合在一起时，它们一直处于静止状态，直到射精。这个过程被称为动力激活。一旦进入女性生殖道，精子就会与子宫和输卵管的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。这种现象与精子的过度激活有关，精子的活力更强，精子通过卵子相关的卵丘和透明带的速度和强度增加，卵子相关的卵丘是一种高度粘稠的富含蛋白多糖的液体，含有连接在一起的卵丘细胞，透明带是排卵前生长的卵母细胞产生的一种相对较厚的细胞外基质。尽管不同的细胞内信号转导通路影响环磷酸腺苷水平、钙离子浓度、pH、蛋白质酪氨酸磷酸化和肌动蛋白重组，但调控获能和精子/卵子相互作用过程的机制尚不完全清楚。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事件，并更好地表征精子如何能够成功地与卵子相互作用、使其受精，并启动一个基因独特的个体的早期发育。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 this 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 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 from the uterus and oviduct, and become fully fertilization competent in a process called capacitation. This phenomenon is associated with the hyperactivation of sperm motility, which is more vigorous, with increased velocity and strength to facilitate sperm passage through egg associated 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 prior to ovulation. The mechanisms regulating the processes of capacitation and sperm/egg interactions are not fully understood, although modification in different intracellular signal transduction pathways affecting cyclic AMP levels, Ca2+ concentration, pH, protein tyrosine phosphorylation, and actin reorganization are known to occur. My research program is devoted to further investigate sperm intracellular events during the acquisition of sperm fertilizing ability and to better characterize how spermatozoa become competent to successfully interact with the egg, fertilize it, and initiate the 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.