Disruption of Mouse CD46 Causes an Accelerated Spontaneous Acrosome Reaction in Sperm

Inoue, Naokazu; Ikawa, Masahito; Nakanishi, Teruyuki; Matsumoto, Misako; Nomura, Midori; Seya, Tsukasa; Okabe, Masaru

doi:10.1128/mcb.23.7.2614-2622.2003

Cited by 128 publications

(106 citation statements)

References 45 publications

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“…Surprisingly, mice carrying a null mutation in the CD46 gene were healthy, females were fully fertile, and male fertility appeared to be facilitated by disruption of the CD46 gene. Indeed, the average number of pups born from CD46 -/ -males was significantly greater than that of wild-type males and the incidence of the spontaneous acrosome reaction doubled in CD46 -/ -sperm, when compared to wild-type sperm (Inoue et al, 2003). These data suggest that CD46 may be involved in regulation of sperm AR (Inoue et al, 2003;Johnson et al, 2007).…”

Section: Discussionmentioning

confidence: 59%

“…It is also known as Human Membrane Cofactor protein (MCP), and it is an ubiquitously expressed protein involved in cell protection from complement attack. In spermatozoa, it has been found on the inner acrosomal membrane (Clift et al, 2009;Inoue et al, 2003). Surprisingly, mice carrying a null mutation in the CD46 gene were healthy, females were fully fertile, and male fertility appeared to be facilitated by disruption of the CD46 gene.…”

Section: Discussionmentioning

confidence: 99%

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Network Analyses of Sperm–Egg Recognition and Binding: Ready to Rethink Fertility Mechanisms?

Bernabò

Ordinelli

Agostino

et al. 2014

OMICS: A Journal of Integrative Biology

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The rapid growth of published literature makes biomedical text mining increasingly invaluable for unpacking implicit knowledge hidden in unstructured text. We employed biomedical text mining and biological networks analyses to research the process of sperm egg recognition and binding (SERB). We selected from the literature the molecules expressed either on spermatozoa or on oocytes thought to be involved in SERB and, using an automated literature search software (Agilent Literature Search), we realized a network, SERBN, characterized by a hierarchical scale free and a small world topology. We used an integrated approach, either based on selection of hubs or by a cluster analysis, to discern the key molecules of SERB. We found that in most cases some of them are not directly situated on spermatozoa and oocyte, but are dispersed in oviductal fluid or embedded in exosomes present in the perivitelline space. To confirm and validate our results, we performed further analyses using STRING and Reactome FI software. Our findings underscore that the fertility is not a property of gametes in isolation, but rather depends on the functional integrity of the entire reproductive system. These observations collectively underscore the importance of integrative biology in exploring biological systems and in rethinking of fertility mechanisms in the light of this innovative approach.

show abstract

Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Network Analyses of Sperm–Egg Recognition and Binding: Ready to Rethink Fertility Mechanisms?

Bernabò

Ordinelli

Agostino

et al. 2014

OMICS: A Journal of Integrative Biology

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show abstract

“…The complement regulator membrane cofactor protein, CD46, appears to regulate the sperm acrosome reaction by stabilizing the acrosomal membrane and facilitates sperm-egg interactions (41).…”

Section: Discussionmentioning

confidence: 99%

Expression profiling reveals meiotic male germ cell mRNAs that are translationally up- and down-regulated

Iguchi

Tobias

Hecht

2006

Proc. Natl. Acad. Sci. U.S.A.

138

145

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T he testis contains a diverse population of somatic and germ cell types. As spermatogenesis proceeds, diploid spermatogonia differentiate into meiotic spermatocytes, which divide twice without additional DNA replication, producing haploid round spermatids (1, 2). These spermatids transform into highly polarized and uniquely shaped spermatozoa. As the germ cells differentiate, the changing amounts and populations of mRNAs in the germ cells and somatic cells have been well documented by microarray analyses (3-7) and by the cloning and sequencing of cDNA libraries prepared from highly purified populations of individual cell types (8,9).Although these microarray and cloning studies provide valuable insight into the temporal appearance͞disappearance of individual mRNAs, they do not address the question of when the proteins encoded by the mRNAs are synthesized. In the germ cells of the testis, a temporal disconnect between mRNA transcription and protein synthesis is especially common, in part because RNA synthesis terminates during midspermiogenesis long before the spermatid completes its differentiation into the spermatozoon (1). Thus, posttranscriptional mechanisms play major roles in the temporal regulation of protein synthesis in developing male gametes.

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“…26 Interestingly, mouse CD46 was found only in testis and the protein was found on the inner acrosomal membrane of sperm. 27 The fact that CD46 is expressed only in testis in various mammalian species indicates the importance of CD46 in reproduction and encouraged us to make a Cd46-disrupted mouse line. Therefore, we produced mice carrying a null mutation in the Cd46 gene.…”

Section: -11mentioning

confidence: 99%

The mechanism of sperm–egg interaction and the involvement of IZUMO1 in fusion

Inoue¹,

Ikawa²,

Okabe³

2010

Asian J Androl

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An average human ejaculate contains over 100 million sperm, but only a few succeed in accomplishing the journey to an egg by migration through the female reproductive tract. Among these few sperm, only one participates in fertilization. There might be an ingenious molecular mechanism to ensure that the very best sperm fertilize an egg. However, recent gene disruption experiments in mice have revealed that many factors previously described as important for fertilization are largely dispensable. One could argue that the fertilization mechanism is made robust against gene disruptions. However, this is not likely, as there are already six different gene-disrupted mouse lines (Calmegin, Adam1a, Adam2, Adam3, Ace and Pgap1), all of which result in male sterility. The sperm from these animals are known to have defective zona-binding ability and at the same time lose oviduct-migrating ability. Concerning spermzona binding, the widely accepted involvement of sugar moiety on zona pellucida 3 (ZP3) is indicated to be dispensable by gene disruption experiments. Thus, the landscape of the mechanism of fertilization is revolving considerably. In the sperm-egg fusion process, CD9 on egg and IZUMO1 on sperm have emerged as essential factors. This review focuses on the mechanism of fertilization elucidated by gene-manipulated animals.

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Disruption of Mouse CD46 Causes an Accelerated Spontaneous Acrosome Reaction in Sperm

Cited by 128 publications

References 45 publications

Network Analyses of Sperm–Egg Recognition and Binding: Ready to Rethink Fertility Mechanisms?

Network Analyses of Sperm–Egg Recognition and Binding: Ready to Rethink Fertility Mechanisms?

Expression profiling reveals meiotic male germ cell mRNAs that are translationally up- and down-regulated

The mechanism of sperm–egg interaction and the involvement of IZUMO1 in fusion

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