Journal of Andrology
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Published-Ahead-of-Print May 23, 2007, DOI:10.2164/jandrol.107.002980

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Structural Alterations of Epididymal Epithelial Cells in Cathepsin A-Deficient Mice Affect the Blood Epididymal Barrier and Lead to Altered Sperm Motility

Louis Hermo *, Nadine Korah , Mary Gregory , Lauren ye Liu , Daniel G Cyr , Alessandra D'Azzo , and Charles E Smith

* To whom correspondence should be addressed. E-mail: louis.hermo{at}mcgill.ca.

Past studies have shown that the epithelial lining of the epididymis in adult mice deficient in cathepsin A (PPCA-/-) becomes swollen and vacuolated as a result of an accumulation of pale lysosomes, some of very large size, in addition to the presence of an abundance of macrophages infiltrating the intertubular spaces. The purpose of this study was to assess the integrity of the epididymal epithelial blood barrier in these altered mice by characterizing the distribution of claudins and the leakiness of tight junctions to lanthanum nitrate. A second goal was to characterize sperm motility behavior in PPCA-/- mice using computer assisted sperm analyses (CASA). The results indicated that lanthanum nitrate penetrated apical junctional complexes between adjacent epithelial cells and entered the epididymal lumen in PPCA-/- mice but not in control PPCA+/+ mice. Distributions of immunostaining for claudins (Cldns) 1, 3, 8 and 10 revealed unique patterns of expression based on cell type and region specificity in PPCA+/+ mice, which were much different in PPCA-/- mice and included reduced intensities of immunoreactions, complete absence of immunoreactions, and appearance of atypical cytoplasmic immunoreactions. CASA indicated that sperm counts in the PPCA-/- mice were 70% reduced and there was a four-fold higher percentage of static sperm in PPCA-/- mice compared to controls among other problems. These results suggest that PPCA deficiency causes structural changes to the blood epididymal barrier as evidenced by lanthanum nitrate and claudin expressions that affects the luminal environment of the epididymis resulting in altered sperm motility.


Key words: Epididymis • Reproductive Tract • Sperm • Spermatogenesis • Testis






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