Spermatozoal maturation in the epididymis is dependent on proteins secreted by the epithelium, and those that create the proper ionic composition and pH of the lumen as well as the blood-epididymal barrier. In the human epididymis, little information exists on the regulation of these proteins in male infertility. Our objectives were to assess gene expression profiles in the caput epididymidis from men with normal spermatogenesis and men with non-obstructive azoospermia. Using microarrays, we identified 414 genes in the caput epididymidis that were differentially regulated in infertile men by at least 2-fold as compared to the fertile. They were mostly involved in transcription, intracellular signaling, immunity and fertility. While the expression of genes encoding tight junctional proteins wasnt affected, the localization of CLDN10 and TJP1, but not CLDNs 1, 3 and 8, was altered in infertile patients suggesting that there may be alterations in the paracellular functions of the blood-epididymal barrier. Differentially regulated genes included several encoding proteins involved in spermatozoal maturation, water and ion channels and beta-defensins: CRISP1, SPINLW1, FAM12B, DEFB129 were upregulated whereas CFTR, AQP5, KCNK7, KCNK17, SLC6A20, SLC13A3, DEFB126, and DEFB106A were downregulated. Furthermore, the immunolocalization of AQP5 but not of CFTR or CRISP1 varied in infertile and fertile patients. The observation that the expression of genes involved in water and ion transport were repressed in infertile patients suggests that these genes are regulated by the presence of testicular products or spermatozoa in the epididymal lumen or are part of a broader syndrome associated with non-obstructive azoospermia.

Written by
Dubé E, Hermo L, Chan PT, Cyr DG.

Reference
Biol Reprod. 2007 Oct 10; [Epub ahead of print]

PubMed Abstract
PMID:17928628

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