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

Abstract

The seminiferous tubules and the excurrent ducts of the mammalian testis are physiologically separated from the mesenchymal tissues and the blood and lymph system by a special structural barrier to paracellular translocations of molecules and particles: the “blood–testis barrier”, formed by junctions connecting Sertoli cells with each other and with spermatogonial cells. In combined biochemical as well as light and electron microscopical studies we systematically determine the molecules located in the adhering junctions of adult mammalian (human, bovine, porcine, murine, i.e., rat and mouse) testis. We show that the seminiferous epithelium does not contain desmosomes, or “desmosome-like” junctions, nor any of the desmosome-specific marker molecules and that the adhering junctions of tubules and ductules are fundamentally different. While the ductules contain classical epithelial cell layers with E-cadherin-based adherens junctions (AJs) and typical desmosomes, the Sertoli cells of the tubules lack desmosomes and “desmosome-like” junctions but are connected by morphologically different forms of AJs. These junctions are based on N-cadherin anchored in cytoplasmic plaques, which in some subforms appear thick and dense but in other subforms contain only scarce and loosely arranged plaque structures formed by α- and β-catenin, proteins p120, p0071 and plakoglobin, together with a member of the striatin family and also, in rodents, the proteins ZO-1 and myozap. These N-cadherin-based AJs also include two novel types of junctions: the “areae adhaerentes”, i.e., variously-sized, often very large cell-cell contacts and small sieve-plate-like AJs perforated by cytoplasm-to-cytoplasm channels of 5–7 nm internal diameter (“cribelliform junctions”). We emphasize the unique character of this epithelium that totally lacks major epithelial marker molecules and structures such as keratin filaments and desmosomal elements as well as EpCAM- and PERP-containing junctions. We also discuss the nature, development and possible functions of these junctions.Electronic supplementary materialThe online version of this article (doi:10.1007/s00441-014-1906-9) contains supplementary material, which is available to authorized users.

Redox status assessment in infertile patients with non‐obstructive azoospermia undergoing testicular sperm extraction: A prospective study

“…Additionally, it was recently demonstrated that mitochondrial ROS generation could trigger autophagy , leading to the accumulation of damaged mitochondria and enhanced ROS production. All the above processes negatively affect blood–testis barrier (BTB) integrity, contributing to distorted spermatogenesis , , …”

“…All the above processes negatively affect blood-testis barrier (BTB) integrity, contributing to distorted spermatogenesis. 42,43,44 On this basis, the primary objective of the present study was to evaluate redox balance in patients with azoospermia, in order to establish the potential role exerted by ROS in the genesis of testicular secretory injury, when NOA occurs. optimize the better therapeutic approach and to counsel properly the infertile patients.…”

The cell–cell junctions of mammalian testes: II. The lamellar smooth muscle monolayer cells of the peritubular wall are laterally connected by vertical adherens junctions—a novel architectonic cell–cell junction system

“…Bovine tissue samples of freshly slaughtered animals were obtained in the regional slaughterhouse (Mannheim, Germany), murine tissue samples (rat and mouse), and guinea pig tissues from mature and sexually active animals kept in the Central Animal Laboratory of the German Cancer Research Center (Heidelberg, Germany; for details see Franke et al 2006Franke et al , 2015Domke et al 2014). Tissue specimens from 3-year-old boars (German landrace pigs) were provided by Dr. Heiner Niemann, head of the Institute of Farm Animal Genetics (Friedrich-Loeffler-Institute, Federal Research Institute for Animal Health, Mariensee, Germany) and fixed as described (Rickelt et al 2011;Domke et al 2014). Human tissue samples were obtained from surgical material taken and processed in compliance with the regulations of the Ethics Committees of the Universities of Heidelberg and Marburg (Germany; see also Franke et al 2006Franke et al , 2015Domke et al 2014).…”

“…In previous studies of mature mammalian testes, we had noted that the epithelium within the seminiferous tubules is fundamentally different from all other epithelia, including those of the testicular excurrent ducts. With respect to the major molecular and ultrastructural components in the mature and healthy seminiferous tubules, it has for example been found that in this stage, the Sertoli and germ cells do not contain any cytokeratin (CK) but only vimentin intermediate-sized filaments (IFs), often organized in bundles enriched in the perinuclear region (Franke et al 1979(Franke et al , 1982b; see also Spruill et al 1983;Paranko and Virtanen 1986; for further references, see Domke et al 2014); do not contain desmosomes or desmosome-like structures, not even any desmosome-specific marker proteins or glycoproteins (Franke et al 1982a;Domke et al 2014; for a list of opposite reports and claims, see ESM, Table S1); do not contain E-cadherin (CDH1)-based but only Ncadherin (CDH2)-based adherens junctions (AJs; Franke et al 1982a;Cyr et al 1992Cyr et al , 1993Newton et al 1993;Byers et al 1994;Domke et al 2014;Domke 2018); and do not contain an apical zonula adhaerens but deep plasma membrane indentations in the apical plasma membranes of the Sertoli cells in which the spermatid heads are embedded (cf. Franke et al 1978a).…”

“…On the other hand, we have recently found that the cells within the seminiferous tubules are connected with each other and with the germ cells by special-often very large-N-cadherin-based AJ-type junctions (Bareae adhaerentes^), which in many regions are characterized by cytoplasmic AJ plaques containing αand β-catenin, proteins p120 and p0071, as well as plakoglobin (Domke et al 2014). Moreover, we have also discovered a very special form of Sertoli cell junctions, the cribelliform junctions (Bareae cribelliformes^), which are characterized by groups of cytoplasm-to-cytoplasm channels of 5-7 nm cytoplasmic width which are laterally connected by short TJ-or AJ-type structures (Domke et al 2014).…”