title: Reduced Fertility and Altered Epididymal and Sperm Integrity in Mice Lacking ADAM7.
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.
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea.
authors.forename: Heejin
authors.initials: H
authors.lastname: Choi
authors.affiliation: 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.
authors.forename: Cecil
authors.initials: C
authors.lastname: Han
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea.
authors.forename: Sora
authors.initials: S
authors.lastname: Jin
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea.
authors.forename: Jun Tae
authors.initials: JT
authors.lastname: Kwon
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea.
authors.forename: Jihye
authors.initials: J
authors.lastname: Kim
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea.
authors.forename: Juri
authors.initials: J
authors.lastname: Jeong
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea.
authors.forename: Jaehwan
authors.initials: J
authors.lastname: Kim
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea.
authors.forename: Sera
authors.initials: S
authors.lastname: Ham
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea.
authors.forename: Suyeon
authors.initials: S
authors.lastname: Jeon
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea yjyoo@gist.ac.kr.
authors.forename: Yung Joon
authors.initials: YJ
authors.lastname: Yoo
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea choch@gist.ac.kr.
authors.forename: Chunghee
authors.initials: C
authors.lastname: Cho
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D004822:Epididymis / Q000473:pathology*; D004847:Epithelial Cells / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D007248:Infertility, Male / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D013075:Sperm Capacitation / Q000235:genetics; D013077:Sperm Head / Q000473:pathology; D013081:Sperm Motility / Q000235:genetics; D013082:Sperm Tail / Q000473:pathology; D013094:Spermatozoa / Q000473:pathology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C492300:Itm2b protein, mouse; D008565:Membrane Proteins; D051722:ADAM Proteins; C484106:Adam7 protein, mouse
keywords: ADAM; epididymis; fertility; gene knockout; male infertility; sperm; sperm maturation