Molecular Mechanism of Functional Regulation of Spermatiogenic Cells by Interaction with Other Somatic Cells and Eggs

生精细胞与其他体细胞和卵子相互作用功能调节的分子机制

基本信息

批准号：
11235201
负责人：
BABA Tadashi
金额：
$ 59.71万
依托单位：
University of Tsukuba
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11235201/
关键词：
Male gamete Cell-to-cell interaction Sperm Sperm maturation Fertilization Sertoli cell Oviduct Spermatogenesis 輪卵管

项目摘要

To elucidate the functional regulation of mouse male gamete by other somatic cells and eggs, we have examined the cell interaction in spermatogenesis, sperm maturation, sperm transit from uterus to oviduct, and fertilization in mouse. The following experimental results have been obtained(1)cDNA clones encoding a testis-specific poly(A) polymerase, TPAP, a candidate molecule responsible for cytoplasmic polyadenylation of pre-existing mRNAs in spermatogenic cells have been identified from a mouse testis cDNA library. Male mice lacking TPAP resulted in the arrest of spermatogenesis and in the increase of apoptosis in spermatogenic cells. The increased apoptosis before the stage of haploid round spermatids may be due not to direct effects of the spermatogenic arrest, but to a transduction of the spoptotic signals to the earlier stages of spermatogenic cells through Sertoli cells.(2)In mouse, two different isoforms of ADAM1. ADAM1a and ADAM1b, are produced in the testis. ADAM1a is restricte … More dly localized within the endoplasmic reticulum of testicular germ cells, whereas epididymal sperm contain only ADAM1b on the plasma membrane. The loss of mouse ADAM1a resulted in the male infertility because of the severely impaired ability of sperm to migrate from the uterus into oviduct through the uterotubal junction. However, epididymal sperm of ADAM1a-deficient mice were capable of fertilizing the cumulus-intact, zona pellucida-intact eggs in vitro, despite the delayed dispersal of cumulus cells and the reduced adhesion/binding to the zona pellucida. These results suggest that the ADAM1a/ADAM2 fertilin complex may regulate the selective transport of specific sperm proteins including ADAM3, which are involved in the migration into the oviduct, in the dispersal of cumulus cells, and in the binding to the zona pellucida, from the endoplasmic reticulum of testicular germ cells onto the cell surface.(3)Male mice lacking sperm PH-20 were still fertile, in spite of a reduced ability to disperse cumulus cells from the cumulus mass. Western blot analysis of sperm extracts revealed the presence of other hyaluronidase(s), except PH-20, presumably within the sperm acrosome. These data provide evidence that PH-20 is not essential for fertilization at least in the mouse, and suggest that the other hyaluronidase(s) may play an important role in the sperm penetration through the cumulus cell layer and/or the egg zona pellucida, possibly in cooperation with PH-20. Less

为了通过其他体细胞和卵阐明小鼠男配子的功能调节，我们检查了细胞相互作用，精子发生，精子成熟，从子宫到产卵的精子转移以及小鼠的受精。已经获得了以下实验结果（1）编码睾丸特异性聚（A）聚合酶TPAP的cDNA克隆TPAP，一种由小鼠testis testis cdna库中鉴定出来，鉴定出了鉴定出，该分子负责鉴定出负责细胞中的细胞质中的细胞质腺苷酸化的候选分子。缺乏TPAP的雄性小鼠导致精子发生和精子生成细胞凋亡的增加。单倍体圆形精子前的凋亡增加可能不是由于精子骤停的直接作用，而是由于将蜘蛛学信号转换为通过Sertoli细胞的早期阶段。（2）在小鼠中，ADAM1的两种不同同种型。 ADAM1A和ADAM1B在睾丸中产生。 ADAM1A是限制性的……更倾向于定位在测定生殖细胞的内质网中，而质膜上仅含有ADAM1B的附子精子。小鼠ADAM1A的丧失导致了男性不育症，因为精子通过子宫颈连接的精子从子宫迁移到产卵的能力严重受损。然而，ADAM1A缺陷小鼠的附子精子能够在体外施肥，Zona pellucida-Intact卵在体外施肥，努力稳定的积云细胞的分散剂，并降低依从性/与Zona Pellucida的结合。 These results suggest that the ADAM1a/ADAM2 fertilin complex may regulate the selective transport of specific sperm proteins including ADAM3, which are involved in the migration into the oviduct, in the dispersal of cumulus cells, and in the binding to the zona pellucida, from the endoplasmic reticulum of testical germ cells onto the cell surface.(3)Male mice lacking sperm PH-20 were still fertile, in spite of从积云质量中分散积云细胞的能力降低。精子提取物的蛋白质印迹分析表明，除pH-20以外的其他透明质酸酶的存在，大概是精子遍布的精子。这些数据提供了证据表明，pH-20至少在小鼠中不是受精至关重要的，并表明其他透明质酸酶在通过Cumulus细胞层和/或Egg Zona pellucida中可能起重要作用，与PH-20合作。较少的