The Blood-Testis and Blood-Epididymis Barriers Are More than Just Their Tight Junctions1

Abstract

The terms blood-testis barrier (BTB) or blood-epididymis barrier (BEB), are often described as Sertoli cell-Sertoli cell tight junctions (TJs) or TJs between the epithelial cells in the epididymis, respectively. However, in reality, the BTB and BEB are much more complex than just the TJ. The focus of this minireview is to remind readers that the complete BTB and BEB are comprised of three components: anatomical, physiological, and immunological. The TJs form the anatomical (physical) barrier that restricts passage of molecules and cells from entering or exiting the lumen. The physiological barrier is comprised of transporters that regulate movement of substances in or out of the lumen, thus creating a microenvironment, which is critical for the proper development and maturation of germ cells. The immunological barrier limits access by the immune system and sequesters the majority of the autoantigenic germ cells. Combined with the overall immune-privilege of the testis, this suppresses detrimental immune responses against the autoantigenic germ cells. These three components on their own do not create a complete functional barrier; instead, it is the interaction between all three components that create a barrier of maximal competence.

Microbiota and the control of blood-tissue barriers

“…21,22 Sertoli cells are highly dynamic, changing their 3-dimensional structure during the course of spermatogenesis and spermiogenesis. 25,26 This causes the BTB to change as well: the TJPs undergo remodeling (opening and closing) to allow the passage of preleptotene spermatocytes from the basal to the adluminal compartment, where they undergo meiosis. 25 This structural disassembly and reassembly of the TJPs occurs at stage VIII in the rat and is tightly regulated by testosterone and cytokines.…”

“…25,26 This causes the BTB to change as well: the TJPs undergo remodeling (opening and closing) to allow the passage of preleptotene spermatocytes from the basal to the adluminal compartment, where they undergo meiosis. 25 This structural disassembly and reassembly of the TJPs occurs at stage VIII in the rat and is tightly regulated by testosterone and cytokines. [27][28][29] Comparison of the BBB and BTB…”

Why are epididymal tumours so rare?

“…56 Of more than 100 tight junction proteins, some are themselves tumour suppressors, 57 whereas others are hubs for signal transduction leading to cell proliferation and tumourigenesis. 58 Tight junctions in the epididymis are the physical component of the blood-epididymis barrier 59 and the major tight-junction proteins have been localized in the human epididymis. 60 When Sertoli cell tight junctions undergo seasonal regression, epididymal tight junctions remain intact in the mink 61,62 and are even reinforced in bats.…”

AKAP9 Is Essential for Spermatogenesis and Sertoli Cell Maturation in Mice

“…Sertoli cells undergo maturation from birth through puberty, with changing gene expression and morphology as they halt proliferation (for review see (Sharpe et al 2003). This differentiation includes the formation of the blood-testis barrier (BTB), separating the mitotic/spermatogonial compartment from the meiotic/spermatocyte compartment (Petersen and Soder 2006;Mital et al 2011). Preleptotene spermatocytes must traverse the BTB, requiring Sertoli cell-regulated disassembly and reassembly of tight and gap junctions (Griswold 1995(Griswold , 1998Cheng and Mruk 2002;Wong and Cheng 2005).…”