Male Mice Deficient for Germ-Cell Cyritestin Are Infertile1

Abstract

Cyritestin is a membrane-anchored sperm protein belonging to the ADAM (f1.gif" BORDER="0"> f2.gif" BORDER="0">isintegrin and f1.gif" BORDER="0"> f3.gif" BORDER="0">etalloprotease) family of proteins, which are proposed to be involved in cell-cell adhesion through binding to integrin receptors. Several lines of evidence support a role of cyritestin and other members of this protein family in the fusion of sperm and the egg plasma membrane. In an effort to elucidate the physiological function of cyritestin, we have disrupted its locus by homologous recombination. Male homozygous null mutants are infertile, even though spermatogenesis, mating, and migration of sperm from the uterus into the oviduct are normal. In vitro experiments showed that infertility is due to the inability of the cyritestin-deficient sperm to bind to the zona pellucida. However, after removal of the zona pellucida, sperm-egg membrane fusion monitored by the presence of pronuclei and generation of 2- and 4-cell embryos did not reveal any differences from the wild-type situation. These results demonstrate that cyritestin is crucial in the fertilization process at the level of the sperm-zona pellucida interaction.

Identification of a hyaluronidase, Hyal5, involved in penetration of mouse sperm through cumulus mass

“…3E). Only ADAM3 among four proteins examined was capable of binding to the ZP tightly, as expected (24,33). Hyal5 also bound to the ZP, but the level of ZP binding was negligibly low.…”

Mechanism of Fertilization: A Modern View

“…ADAM2 had a function in testis to form a dimer with testicular ADAM1a (not with sperm ADAM1b), which functions to present ADAM3 on spermatozoa [42]. (ADAM3 is a protein that is required for spermatozoa to exhibit fertilization competency [49]. )…”

“…We refer to this group as Class I; all spermatozoa from this group were shown to lack ADAM3 (or have aberrant ADAM3). Since the Adam3-disrupted male mice are infertile and produce spermatozoa with a Class I phenotype [49] aDaM3 was considered to function as an ultimately essential factor in all gene-disrupted mouse lines with Class I phenotype. The gene-disrupted mouse lines with Class I phenotype are listed in Table 3.…”

Anchoring Junctions As Drug Targets: Role in Contraceptive Development

“…Although mice lacking ADAM2 are viable and healthy, they were shown to be infertile (Cho et al, 1998). Likewise, male mice lacking ADAM3 (cyritestin) were also infertile (Shamsadin et al, 1999;Nishimura et al, 2001), illustrating that ADAMs are critical to spermatogenesis and fertility.…”