Testicular and epididymal ADAMs: expression and function during fertilization

Abstract

The disintegrin and metalloprotease domain-containing protein (ADAM) family of multidomain membrane proteins comprises at least 34 members in mammals. More than half of these proteins are expressed specifically or predominantly in mammalian testes and epididymis, implying their prominence in male reproduction. These reproductive ADAMs can be classified into three phylogenetic groups; designated I, II, and III. Each group displays remarkably contrasting features. Group I contains 11 ADAMs expressed in the testis. The genes that encode these proteins lack introns in their coding sequences and most of the proteins are processed into prodomain-lacking forms in mature sperm. Five ADAMs--encoded by genes with multiple exons and introns--belong to phylogenetic group II. These ADAMs are also expressed in testicular germ cells, but both prodomains and metalloprotease domains are lacking in mature sperm. Two phylogenetic group III ADAMs are synthesized in the epididymis; one of which is secreted and transferred to the sperm surface. Some of these sperm ADAMs are assembled into potentially functional complexes, including ADAM1B-ADAM2, ADAM2-ADAM3-ADAM4, ADAM2-ADAM3-ADAM5, and ADAM2-ADAM3-ADAM6. It has been suggested that ADAM2 and ADAM3 have roles in sperm-egg interactions. Mouse knockout studies have revealed that the ADAM2-ADAM3 complex is critical for in vivo sperm migratory function in the female reproductive tract.