A human sperm antigen possibly involved in binding and/or fusion with zona-free hamster eggs

Okabe, Masaru; Nagira, Morio; Kawai, Yuichi; Matzno, Sumio; Matsui, Tsutomu; Mayumi, Tadanori

doi:10.1016/s0015-0282(16)54015-1

Cited by 75 publications

(54 citation statements)

References 16 publications

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“…25 In fact, several anti-human CD46 monoclonal antibodies effectively inhibit fertilization in in vitro fertilization. 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.…”

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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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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“…These include its sperm-dominant high expression of protein [14,15], its lack of charged sugars [16,17], its limited distribution to the inner acrosomal membrane until the acrosomal reaction, when it is expressed on the surface of sperm [18], and its deficiency possibly being related to ideopathic infertility [47]. In addition, although monoclonal antibodies against CD46 were reported to block human sperm binding to hamster eggs or to human eggs [18,19], the inhibition of binding was always incomplete. Furthermore, the epitopes recognized by monoclonal antibodies competent to block sperm binding to human and hamster eggs are wholly different [18,19].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, although monoclonal antibodies against CD46 were reported to block human sperm binding to hamster eggs or to human eggs [18,19], the inhibition of binding was always incomplete. Furthermore, the epitopes recognized by monoclonal antibodies competent to block sperm binding to human and hamster eggs are wholly different [18,19]. Although the role of CD46 in fertilization has not been established definitively, we propose that the novel mechanism of CD46 gene regulation and its tissue-specific expression in the testicular germ cells supports this putative role of CD46.…”

Section: Discussionmentioning

confidence: 99%

“…One possible interpretation of these findings is that sperm CD46 may act as an egg-binding protein expressed on the inner acrosomal membrane. The fact that monoclonal antibodies against human CD46 partially block binding of human sperm and hamster eggs may support this hypothesis [18,19]. Although conclusive evidence has yet to be discovered, CD46 may be involved in homologous Figure 1 For legend see facing page species recognition by functioning in C-immune effector cell responses (innate immunity) and in sperm-egg adhesion (fertilization).…”

Section: Introductionmentioning

confidence: 99%

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Identification and characterization of a silencer regulatory element in the 3′-flanking region of the murine CD46 gene

Nomura

Tsujimura

Begum

et al. 2000

Biochemical Journal

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The murine membrane cofactor protein (CD46) gene is expressed exclusively in testis, in contrast to human CD46, which is expressed ubiquitously. To elucidate the mechanism of differential CD46 gene expression among species, we cloned entire murine CD46 genomic DNA and possible regulatory regions were placed in the flanking region of the luciferase reporter gene. The reporter gene assay revealed a silencing activity not in the promoter, but in the 3´-flanking region of the gene and the silencer-like element was identified within a 0.2-kb region between 0.6 and 0.8kb downstream of the stop codon. This silencer-like element was highly similar to that of the pig MHC class-I gene. The introduction of a mutation into this putative silencer element of murine CD46 resulted in an abrogation of the silencing effect. Electrophoretic mobility-shift assay indicated the presence of the binding molecule(s) for this silencer sequence in murine cell lines and tissues. A size difference of the protein–silencer-element complex was observed depending upon the solubilizers used for preparation of the nuclear extracts. A mutated silencer sequence failed to interact with the binding molecules. The level of the binding factor was lower in the testicular germ cells compared with other organs. Thus the silencer element and its binding factor may play a role in transcriptional regulation of murine CD46 gene expression. These results imply that the effects of the CD46 silencer element encompass the innate immune and reproductive systems, and in mice may determine the testicular germ-cell-dominant expression of CD46.

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“…The pellet was washed twice in mBWW medium containing 0.3% human serum albumin (HSA) and then resuspended in mBWW medium containing 3.5% HSA at a sperm concentration of 40 Â 10 6 =mL. The Acrobeads test was performed according to the method described previously [8], using immunobeads coated with MH61 monoclonal antibody [14] (MH61-beads), which binds to the anterior portion of acrosome-reacted sperm. One hundred microliters of prepared sperm suspension was divided into a 96-well tissue culture plate (Corning, Corning, NY, USA).…”

Section: Methodsmentioning

confidence: 99%