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Biol Reprod. 2015 Sep;93(3):70. doi: 10.1095/biolreprod.115.130252. Epub 2015 Aug 5.

Reduced Fertility and Altered Epididymal and Sperm Integrity in Mice Lacking ADAM7.

Author information

1
School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea.
2
School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
3
School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea yjyoo@gist.ac.kr.
4
School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea choch@gist.ac.kr.

Abstract

The mammalian epididymis is a highly convoluted tubule that connects the testis to the vas deferens. Its proper functions in sperm transport, storage, and maturation are essential for male reproduction. One of the genes predominantly expressed in the epididymis is ADAM7 (a disintegrin and metalloprotease 7). Previous studies have shown that ADAM7 synthesized in the epididymis is secreted into the epididymal lumen and is then transferred to sperm membranes, where it forms a chaperone complex that is potentially involved in sperm fertility. In this study, we generated and analyzed mice with a targeted disruption in the Adam7 gene. We found that the fertility of male mice was modestly but significantly reduced by knockout of Adam7. Histological analyses revealed that the cell heights of the epithelium were dramatically decreased in the caput of the epididymis of Adam7-null mice, suggesting a requirement for ADAM7 in maintaining the integrity of the epididymal epithelium. We found that sperm from Adam7-null mice exhibit decreased motility, tail deformation, and altered tyrosine phosphorylation, indicating that the absence of ADAM7 leads to abnormal sperm functions and morphology. Western blot analyses revealed reduced levels of integral membrane protein 2B (ITM2B) and ADAM2 in sperm from Adam7-null mice, suggesting a requirement for ADAM7 in normal expression of sperm membrane proteins involved in sperm functions. Collectively, our study demonstrates for the first time that ADAM7 is required for normal fertility and is important for the maintenance of epididymal integrity and for sperm morphology, motility, and membrane proteins.

KEYWORDS:

ADAM; epididymis; fertility; gene knockout; male infertility; sperm; sperm maturation

PMID:
26246218
DOI:
10.1095/biolreprod.115.130252
[Indexed for MEDLINE]

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