Orchestration of occludins, claudins, catenins and cadherins as players involved in maintenance of the blood-epididymal barrier in animals and humans

Abstract

Although spermatozoa are formed during spermatogenesis in the testis, testicular spermatozoa are immature and cannot swim or fertilize. These critical spermatozoal functions are acquired in the epididymis where a specific luminal environment is created by the blood-epididymal barrier; proteins secreted by epididymal principal cells bind to maturing spermatozoa and regulate the maturational process of the spermatozoa. In the epididymis, epithelial cell-cell interactions are mediated by adhering junctions, necessary for cell adhesion, and by tight junctions, which form the blood-epididymal barrier. The regulation of these cellular junctions is thought to represent a key determinant in the process of sperm maturation within the epididymis. Tight junctions between adjacent principal cells permit the formation of a specific microenvironment in the lumen of the epididymis that is essential for sperm maturation. Although we have made significant progress in understanding epididymal function and the blood-epididymal barrier, using animal models, there is limited information on the human epididymis. If we are to understand the normal and pathological conditions attributable to human epididymal function, we must clearly establish the physiological, cellular and molecular regulation of the human epididymis, develop tools to characterize these functions and develop clinical strategies that will use epididymal functions to improve treatment of infertility.

The cell–cell junctions of mammalian testes: I. The adhering junctions of the seminiferous epithelium represent special differentiation structures

“…In all species examined, we used tissue samples from various portions of the excurrent ducts, which are known to contain typical simple or columnar epithelia, as controls of the methods applied and to determine the specificity of the antibodies used in immunocytochemistry of the seminiferous tubules (for references, see, e.g., Dym 1974, 1976, 1977; Kasper and Stosiek 1989; Cyr et al 1995, 2007; Piomboni 1997; Pelletier 2001; DeBellefeuille et al 2003). Frequently, it was possible for us to study testicular tissue containing seminiferous tubules in parallel with preparations of excurrent duct tissues, including the epididymis, from the same animal.…”

Role of MicroRNAs in Controlling Gene Expression in Different Segments of the Human Epididymis

“…Among mRNA targets that were negatively correlated with the levels of their corresponding miRNAs, Cldn10 was particularly interesting with regards to epididymal function and fertility [1], [59]. Cldn10 has been shown to be involved in the paracellular transport of cations across epithelial tight junctions [60], [61] and is expressed in tight junctions of the human epididymis [1], [59].…”

Alterations in the Human Blood-Epididymis Barrier in Obstructive Azoospermia and the Development of Novel Epididymal Cell Lines from Infertile Men1

“…There is surprisingly limited information about the hormones and intracellular signaling pathways implicated in the formation and maintenance of the blood-epididymis barrier [23]. Because the IHCE1 cells do not form functional tight junctions, we compared gene expression profiles with human epididymal principal cells (FHCE1) that were derived from a fertile patient and were shown to form functional tight junctions, in order to identify regulatory pathways that may be implicated in the regulation of epididymal tight junctions [37].…”

“…Tight junctions are composed of integral proteins such as occludin (OCLN), tricellulin, and a larger family of proteins, the claudins (CLDNs) [22,23]. It has previously been reported that the rat and human epididymis contain a large number of CLDNs [24][25][26][27][28].…”