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Testicular and epididymal ADAMs: expression and function during fertilization

Nature Reviews Urology volume 9, pages 550–560 (2012)Cite this article

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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.

Key Points

  • Male reproductive ADAMs are divided phylogenetically into three major groups; group I (intronless testicular genes), group II (testicular genes with multiple exons and introns), and group III (epididymal genes)

  • Most of the testicular ADAM proteins are synthesized in spermatogenic cells as precursors and processed to mature forms that are present on the surface of mature sperm

  • Some of the ADAMs that are present in sperm form complexes, such as ADAM1B-ADAM2, ADAM2-ADAM3-ADAM4, ADAM2-ADAM3-ADAM5, and ADAM2-ADAM3-ADAM6

  • Sperm ADAM complexes containing ADAM2 and ADAM3 are active during sperm–egg interactions in vitro and promote sperm migration from the uterus to the oviduct in mice

  • The ability to select sperm with optimal localization patterns and expression levels of ADAMs or develop agonists that promote ADAM function could lead to improved IVF outcomes

  • Continuing studies of sperm ADAMs should provide important information regarding the molecular mechanisms underlying mammalian fertilization

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Figure 1: Phylogeny, tissue expression, genomic organization, and metalloprotease activity of the mammalian ADAM family members.
Figure 2: Localization, complex formation, and processing of reproductive ADAM proteins in mice.
Figure 3: The expression levels of ADAMs in testicular spermatogenic cells and mature sperm of Adam-knockout mice.64,66,74,76,77,78,79
Figure 4: Schematic model summarizing the role of individual mouse ADAMs in sperm function during the various stages of fertilization.

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GenBank/EMBL/DDBJ

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Acknowledgements

The author thanks Boyeon Lee, Jun Tae Kwon, and Heejin Choi for help with manuscript preparation. This work was supported by Korea Science and Engineering Foundation Grant 2010-0028776, Korea Research Foundation Grant KRF-2008-313-C00736, and Gwangju Institute of Science and Technology Systems Biology Infrastructure Establishment Grant.

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  1. School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, 500-712, Korea

    Chunghee Cho

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Cho, C. Testicular and epididymal ADAMs: expression and function during fertilization. Nat Rev Urol 9, 550–560 (2012). https://doi.org/10.1038/nrurol.2012.167

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