Decreased <i>in vitro</i> fertilization efficiencies in the presence of specific cyritestin peptides

Linder, Britta; Heinlein, Uwe A.O.

doi:10.1046/j.1440-169x.1997.t01-1-00013.x

Cited by 56 publications

(41 citation statements)

References 20 publications

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“…In contrast to ADAM6 and ADAM15, which are widely expressed (Frayne et al, 1997), both fertilin ␤ and cyritestin/ADAM3 are spermatogenic cell-specific (Heinlein et al, 1994), are expressed as a large precursor (Linder et al, 1995;Yuan et al, 1997), and each has a potential integrin ligand binding site in the disintegrin domain. Peptide mimetics as inhibitors and antibodies directed to active binding sites of fertilin ␤ and cyritestin/ADAM3 were shown to inhibit sperm-egg binding (Yuan et al, 1997;Linder and Heinlein, 1997). Experimental evaluation of the ADAM-integrin role in cell-cell adhesion can also be explored by using the PSG-Sertoli cell coculture system.…”

Section: Discussionmentioning

confidence: 99%

Chronological gene expression of ADAMs during testicular development: Prespermatogonia (gonocytes) express fertilin β (ADAM2)

Rosselot

Kierszenbaum

Rivkin

et al. 2003

Developmental Dynamics

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Immediately after birth, primordial germinal cell-derived prespermatogonia (PSG), located in the center of the testicular cords, migrate between adjacent Sertoli cells to establish contact with the cord basal lamina. PSG migration suggests continued assembly and disassembly of cell-cell contacts by a molecular mechanism that may involve integrins and their ligands, the disintegrin domain of spermatogenic cell-specific plasma membrane proteins called ADAMs. We have analyzed the temporal gene expression of selected ADAMs in intact fetal, early postnatal, and pubertal rat testis and Sertoli-spermatogenic cell cocultures by reverse transcriptase-polymerase chain reaction, in situ hybridization, and immunocytochemistry. We report that several ADAM transcripts are expressed in fetal, neonatal, and prepubertal testes. Cyritestin (ADAM3), ADAM5, ADAM6, and ADAM15 are expressed in day 17 fetal testes. In contrast, no expression of fertilin ␣ (ADAM1) and fertilin ␤ (ADAM 2) was detected in fetal testes. Fertilin ␤ gene expression starts after postnatal day 2, subsequent to the expression of fertilin ␣, which occurs on postnatal day 1. After postnatal day 2, all the indicated ADAMs, including the fertilin ␣ and fertilin ␤, continue to be expressed. Transcripts of spermatogenic cell-specific fertilin ␣, fertilin ␤, ADAM3, and ADAM5 were detected during the coculture of PSG with Sertoli cells for up to 72 hr after plating. The presence of fertilin ␤ mRNA and protein in cocultured PSG was visualized by in situ hybridization and immunocytochemistry, respectively. These observations indicate that PSG in coculture with Sertoli cells provide a suitable approach for analyzing cell-cell adhesive responses involving spermatogenic cell-specific ADAMs.

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Section: Discussionmentioning

confidence: 99%

Chronological gene expression of ADAMs during testicular development: Prespermatogonia (gonocytes) express fertilin β (ADAM2)

Rosselot

Kierszenbaum

Rivkin

et al. 2003

Developmental Dynamics

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“…These data regarding fertilin ␣ differ from those regarding several other ADAMs. Adhesive events mediated by ADAMs such as fertilin ␤ (24 -27), cyritestin (8,28), ADAM9 (6,29), ADAM15 (31), and ADAM23 (7) are inhibited by peptides corresponding to the sequences in the putative disintegrin loops of these ADAMs. Additional studies of the interactions of fertilin ␤ with eggs (4) and of ADAM15 with ␤ 3 -transfected CHO cells (30) suggest that the disintegrin loops of these proteins are the key (and perhaps only) adhesion-mediating sequences involved in these particular interactions.…”

Section: Discussionmentioning

confidence: 99%

“…4 and 5). Disintegrin loop peptide sequences inhibit disintegrin-mediated adhesion in studies of other ADAMs (fertilin ␤ (24 -27), cyritestin (8,28), ADAM9 (6,29), ADAM15 (15,30), and ADAM23 (7)), and we therefore wanted to verify that the a-1 amino acid sequence had no inhibitory effect on recombinant fertilin ␣ binding by using a BAP-presented peptide form of the a-1 sequence. We surmised that the BAP-presented peptide form could be more effective than the synthetic peptide form, based on our studies of fertilin ␤ (4).…”

Section: Effects Of Different Recombinant Forms Of Fertilin ␣ Onmentioning

confidence: 99%

Analysis of Fertilin α (ADAM1)-mediated Sperm-Egg Cell Adhesion during Fertilization and Identification of an Adhesion-mediating Sequence in the Disintegrin-like Domain

Wong

Zhu²,

Prater³

et al. 2001

Journal of Biological Chemistry

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Fertilin ␣ (also known as ADAM1) is a member of the ADAM (A disintegrin and A metalloprotease domain) family of proteins. In this study, we examine the mechanism of mouse fertilin ␣'s in adhesion of sperm to the egg plasma membrane during fertilization. We find that recombinant forms of fertilin ␣ corresponding to either the disintegrin-like domain or the cysteine-rich domain and the EGF-like repeat can perturb sperm-egg binding, suggesting that both of these domains can participate in fertilin ␣-mediated adhesion events. In further examination of the fertilin ␣ disintegrin-like domain, we find that a subdomain of disintegrin-like domain with the sequence DLEECDCG outside the putative disintegrin loop but with homology to the fertilin ␤ disintegrin loop can inhibit the binding of both sperm and recombinant fertilin ␣ to eggs, suggesting that this is an adhesionmediating motif of the fertilin ␣ disintegrin-like domain. This sequence also inhibits the binding of recombinant fertilin ␤ to eggs and thus is the first peptide sequence found to block two different sperm ligands. Finally, a monoclonal antibody to the tetraspanin protein CD9, KMC.8, inhibited the binding of recombinant fertilin ␣ to eggs in one type of binding assay, suggesting that, under certain conditions, fertilin ␣ may interact with a KMC.8-sensitive binding site on the egg plasma membrane. ADAM1 (for A disintegrin and A metalloprotease) proteins comprise a recently identified and rapidly growing molecular family of membrane proteins. To date, ϳ30 ADAMs have been identified in a variety of animal species, including several mammals, Xenopus laevis, Drosophila melanogaster, and Caenorhabditis elegans (1, 2). The conserved domain structure of ADAMs (see Fig. 1A) and functional analyses of these proteins indicate that members of this family have functions as proteases and/or as cell adhesion molecules. In the ADAMs that have been described to function as cell adhesion molecules, the adhesive activity generally appears to be attributable to the disintegrin-like domain, a domain with homology to integrin ligand-like snake venom polypeptides. These venom polypeptides, known as disintegrins, contain an RGD tripeptide, presented at the end of an extended loop structure called the "disintegrin loop" (3). Although ADAMs share significant sequence homology in their disintegrin-like domains to snake venom disintegrins, they do not have RGD sequences in their putative disintegrin loops (with the exception of human ADAM15). Various studies have shown that the adhesion-mediating sequence of several ADAMs appears to be a short sequence within the putative disintegrin loop, such as the ECDcontaining sequences in fertilin ␤ (4, 5), ADAM9 (6), and ADAM23 (7), or the QCD-containing sequence in cyritestin (8).Among the cell adhesion events that are mediated by ADAMs are the interactions between mammalian gamete plasma membranes during fertilization. On mouse sperm, there are at least three ADAMs that appear to participate in sperm-egg binding: fertilin ␣ (ADAM1), fertili...

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“…We have recently reported very similar findings in the case of the human tMDC I gene, which is also non-functional in the human [17]. Taken together with the absence of a functional human fertilin α gene [18,19], it is now apparent that three of the five MDC proteins abundantly expressed in the testes of non-human primates and located on mature caudal sperm [10] are not expressed in the human, despite the substantial experimental data implicating two of these proteins (fertilin α and tMDC I) in sperm-egg interactions in rodent systems [5][6][7]13,14]. Such a finding is in keeping with our recently proposed hypothesis [23] that sperm-egg interactions involve many sperm proteins which act co-operatively, but are not absolutely essential.…”

Section: Discussionmentioning

confidence: 99%

“…However, recent studies on a fertilin β knockout mouse [12] have demonstrated that, while fertilin β-null males have greatly decreased fertility, this could be largely attributed to causes other than impaired oolemma binding, supporting the view that other MDC proteins may be equally, if not more, important in sperm-egg interactions. Indeed, recent in itro studies on mouse tMDC I have supported a role for this protein in rodent sperm-egg interactions [13,14]. For practical reasons, virtually all in itro studies aimed at establishing a role for disintegrin-integrin interactions in spermegg recognition have utilized rodent model systems.…”

Section: Introductionmentioning

confidence: 99%

Transcripts encoding the sperm surface protein tMDC II are non-functional in the human

Frayne

DIMSEY

Jury

et al. 1999

Biochemical Journal

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Five members of the MDC (metalloproteinase-like,disintegrin-like cysteine-rich domain) family of proteins (fertilin α, fertilin β, tMDC I, tMDC II and tMDC III) are expressed on the surface of macaque (Macaca fascicularis) sperm, where they have been proposed to play a role in sperm-egg binding via an interaction between their disintegrin-like domain and one or more integrins on the egg plasma membrane. Of these, two (fertilin α and tMDC I) have recently been shown to be non-functional in the human. Here we report the existence of multiple isoforms of human tMDC II transcripts in the human, all of which are also non-functional owing to the presence of deletions and in-frame termination codons, when compared with the macaque orthologue, a finding which is further supported by the lack of immunoreactivity on Western blots of human testis and sperm extracts probed with a macaque anti-tMDC II polyclonal antiserum. These results are discussed in the context of our proposed model for multiple proteins implicated in sperm-egg interactions.

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Decreased in vitro fertilization efficiencies in the presence of specific cyritestin peptides

Cited by 56 publications

References 20 publications

Chronological gene expression of ADAMs during testicular development: Prespermatogonia (gonocytes) express fertilin β (ADAM2)

Chronological gene expression of ADAMs during testicular development: Prespermatogonia (gonocytes) express fertilin β (ADAM2)

Analysis of Fertilin α (ADAM1)-mediated Sperm-Egg Cell Adhesion during Fertilization and Identification of an Adhesion-mediating Sequence in the Disintegrin-like Domain

Transcripts encoding the sperm surface protein tMDC II are non-functional in the human

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