Fertilization defects in sperm from mice lacking fertilin beta. Science

Section of Molecular and Cellular Biology, University of California, Davis, CA 95616, USA.
Science (Impact Factor: 33.61). 10/1998; 281(5384):1857-9.
Source: PubMed


Fertilin, a member of the ADAM family, is found on the plasma membrane of mammalian sperm. Sperm from mice lacking fertilin beta were shown to be deficient in sperm-egg membrane adhesion, sperm-egg fusion, migration from the uterus into the oviduct, and binding to the egg zona pellucida. Egg activation was unaffected. The results are consistent with a direct role of fertilin in sperm-egg plasma membrane interaction. Fertilin could also have a direct role in sperm-zona binding or oviduct migration; alternatively, the effects on these functions could result from the absence of fertilin activity during spermatogenesis.

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    • "ADAM1 and ADAM2 form heterodimer, and further with ADAM3 to form fertilin. Knockout of one gene encoding ADAM1A, ADAM1B, ADAM2, or ADAM3 caused sperm damage during the mouse fertilization process (Cho et al., 1998). ADAM7 can form a complete plasma membrane protein in the sperm, and form a complex in sperm capacitation process with calnexin, head shock protein 5 and integral membrane protein 2B (Han et al., 2011). "
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    ABSTRACT: The ADAM (a disintegrin and metalloprotease) family plays an important role in sperm and egg fusion, development, inflammation, adhesion and migration. ADAM10 and ADAM17 are involved in the spermatogenesis. To better understand the role of ADAM10 and ADAM17 in the Chinese mitten crab, Eriocheir sinensis, the full-length cDNAs of ADAM10 and ADAM17 were cloned, and named Es-ADAM10 and Es-ADAM17, respectively. Sequence and structural analysis showed that Es-ADAM10 and Es-ADAM17 have the typical structure of the ADAM family. Quantitative real-time reverse transcription polymerase chain reaction analysis showed that Es-ADAM10 and Es-ADAM17 mRNAs were distributed in the heart, hepatopancreas, intestines, brain, muscle, thoracic ganglia, hemolymph, stomach, testis, ovary, gill and accessory gland. Both mRNAs were highly expressed in the muscles, and relatively high in the testis, ovary and accessory gland. In addition, the Es-ADAM17 mRNA level was detected in every stage of testis development, being relatively high from July to September, the lowest during October and November, increasing from December to January, and reached a peak in January. By contrast, the expression of Es-ADAM10 mRNA was constant during testis development. Immunofluorescence further showed that Es-ADAM10 and Es-ADAM17 proteins were present in the cytoplasm and cytomembrane of spermatocytes, and both detected in the sperm. Furthermore, etoposide induced upregulation of Es-ADAM17 and Es-ADAM10 at both the mRNA and protein levels. This study first showed that Es-ADAM10 and Es-ADAM17 were also involved in the spermatogenesis and mainly participated in the later germ cell apoptosis in E. sinensis. Copyright © 2015. Published by Elsevier B.V.
    Gene 02/2015; 562(1). DOI:10.1016/j.gene.2015.02.060 · 2.14 Impact Factor
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    • "It is involved in sperm-oocyte membrane adhesion and is similar to fertilin; it also uses its disintegrin loop for adhesion. Cyritestin gene knockout mice did not show any defect in sperm-oocyte membrane fusion, but they did show impairment in sperm-zona binding [84]. However, as human cyritestin gene is nonfunctional illustrating the risk of using rodents as models of human/primate fertility. "
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    ABSTRACT: The rapidly increasing global population has bowed the attention of family planning and associated reproductive health programmes in the direction of providing a safe and reliable method which can be used to limit family size. The world population is estimated to exceed a phenomenal 10 billion by the year 2050 A.D., thus presenting a real jeopardy of overpopulation with severe implications for the future. Despite the availability of contraceptive methods, there are over one million elective abortions globally each year due to unintended pregnancies, having devastating impact on reproductive health of women worldwide. This highlights the need for the development of newer and improved contraceptive methods. A novel contraceptive approach that is gaining substantial attention is "immunocontraception" targeting gamete production, gamete outcome, or gamete function. Amongst these, use of sperm antigens (gamete function) seems to be an exciting and feasible approach. However, the variability of immune response and time lag to attain titer among vaccinated individuals after active immunization has highlighted the potential relevance of preformed antibodies in this league. This review is an attempt to analyze the current status and progress of immunocontraceptive approaches with respect to their establishment as a future fertility control agent.
    BioMed Research International 07/2014; 2014(12):868196. DOI:10.1155/2014/868196 · 2.71 Impact Factor
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    • "In vivo, ADAM2 null mice have a fertility rate 50 times lower than the wild-type. This drop in fertility once again does not appear to be the result of a single process, but is instead a combination of deficiencies in sperm-egg fusion, sperm-egg binding, spermZP binding and sperm migration (Cho et al., 1998). ADAM1a knockouts result in sperm unable to migrate to the egg; in vivo the knockout produces an infertile phenotype but in vitro, sperm are able to fertilize eggs. "
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    ABSTRACT: The objective of the present study is to provide a comprehensive in silco sequence analyses of sperm-surface ADAM genes using the curated and nonredundant RefSeq database. 36 complete refseq CDS (coding sequence) of 9 members of ADAM gene family namely ADAM1,2,3,4,5,6,18,24 and 32 were obtained to investigate its evolution and differentiation within and among species. Among the 9 sperm-surface genes ADAM1 has the longest CDS length, the highest GC% and largest variation in base composition. Measurement of polymorphism and genetic diversity (e.g. Number of haplotypes, nucleotide diversity (π) and average number of nucleotide diversity) varied greatly among the sperm-surface ADAM genes. These large variations are evidence for the effect of selection pressure on these genes. The phylogenetic analysis displayed clearly the resolved relationship of sperm-surface ADAM genes and most of bootstrap support were high. Sperm-surface ADAM genes were classified into 6 clades where, ADAM1,2,3,4,5,6,18,24 and ADAM32 of B.taurus and H. sapiens categorizing to one large lineage where ADAM32 of R. norvegicus and M. musculus belonging to another separate lineage. In conclusion, the in silico analysis of the 9 sperm-surface ADAM genes showed a great deal of variation among and within this genes indicating the presence of localized signals of selection pressure on these genes. Moreover, ADAM1,4,6 and 24 have no human orthologues. More importantly, our results suggested that ADAM1,2,3,4,5,6, 18,24 and ADAM32 of B.taurus and H. sapiens were descendent form one ancient ancestor, where ADAM32 of R. norvegicus and M. musculus have another ancestor.
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