Intracellular signalling events leading to sperm fertilization competence

导致精子受精能力的细胞内信号事件

• 批准号: 204880-2013
• 负责人: Leclerc, Pierre
• 金额: $ 1.82万
• 依托单位: Université Laval
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=523564
• 关键词: Intracellular; signalling; events; leading; sperm

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.

精子是高度分化的细胞，其唯一的作用是使卵子受精以产生新的个体。为了实现这一目标，精子由两个不同的隔室连接在一起组成：头部包含一半的父亲遗传内容，鞭毛是将遗传内容与卵子接触所需的移动器官。虽然在睾丸出口处精子的结构是完整的，但在附睾运输过程中，精子细胞获得了移动和与排卵的卵子相互作用的能力。然而，它们保持不动，直到射精，当它们与精囊和前列腺的分泌物混合时。这个过程被称为运动激活。一旦进入雌性生殖道，精子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完全具有受精能力。这种现象与精子运动性的过度激活有关，精子运动性更强，速度和强度增加，以促进精子通过卵相关卵丘，一种含有连接在一起的卵丘细胞的富含蛋白多糖的高粘性液体，以及透明质膜，一种由排卵前生长的卵母细胞产生的相对较厚的细胞外基质。尽管已知会发生影响环AMP水平、Ca 2+浓度、pH、蛋白酪氨酸磷酸化和肌动蛋白重组的不同细胞内信号转导途径的修饰，但调节获能和精子/卵子相互作用过程的机制尚未完全了解。我的研究项目致力于进一步研究精子在获得精子可再生性过程中的细胞内事件，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遇到的生育问题产生影响，在依赖成功繁殖的农业行业（乳制品，肉类）中，最终在人类中，生活方式和环境对男性生育力有很大影响。