Extracellular Matrix: Recent Advances on Its Role in Junction Dynamics in the Seminiferous Epithelium During Spermatogenesis1

Abstract

Spermatogenesis takes place in the seminiferous epithelium of the mammalian testis in which one type A1 spermatogonium (diploid, 2n) gives rise to 256 spermatids (haploid, 1n). To accomplish this, developing germ cells, such as preleptotene and leptotene spermatocytes, residing in the basal compartment of the seminiferous epithelium must traverse the blood-testis barrier (BTB) entering into the adluminal compartment for further development into round, elongating, and elongate spermatids. Recent studies have shown that the basement membrane in the testis (a modified form of extracellular matrix, ECM) is important to the event of germ cell movement across the BTB because proteins in the ECM were shown to regulate BTB dynamics via the interactions between collagens, proteases, and protease inhibitors, possibly under the regulation of cytokines. While these findings are intriguing, they are not entirely unexpected. For one, the basement membrane in the testis is intimately associated with the BTB, which represents the basolateral region of Sertoli cells. Also, Sertoli cell tight junctions (TJs) that constitute the BTB are present side-by-side with cell-cell actin-based adherens junctions (AJ, such as basal ectoplasmic specialization [ES]) and intermediate filament-based desmosome-like junctions. As such, the relative morphological layout between TJs, AJs, and desmosome-like junctions in the seminiferous epithelium is in sharp contrast to other epithelia where TJs are located at the apical portion of an epithelium or endothelium, furthest away from ECM, to be followed by AJs and desmosomes, which in turn constitute the junctional complex. For another, anchoring junctions between a cell epithelium and ECM found in multiple tissues, also known as focal contacts (or focal adhesion complex, FAC, an actin-based cell-matrix anchoring junction type), are the most efficient junction type that permits rapid junction restructuring to accommodate cell movement. It is therefore physiologically plausible, and perhaps essential, that the testis is using some components of the focal contacts to regulate rapid restructuring of AJs between Sertoli and germ INTRODUCTIONDuring spermatogenesis, preleptotene and leptotene spermatocytes residing at the basal compartment of the seminiferous epithelium adjacent to the basement membrane must traverse the blood-testis barrier (BTB) at late stage VIII through early stage IX of the epithelial cycle, entering the adluminal compartment for further development ( Figs. 1 and 2) [1][2][3]. These primary spermatocytes continue to differentiate into round, elongating, and eventually elongate spermatids while moving to the luminal edge of the epithelium and to be released into the tubule lumen at spermiation [2]. These events of cell movement across the seminiferous epithelium are also associated with extensive remodeling of actin-based cell-cell and cell-matrix anchoring junctions, also known as adherens junctions (AJs) and focal contacts, respectively; as well as intermediate filament-based ...

Testis morphology in rats chronically treated with letrozole, an aromatase inhibitor

“…The basement membrane is modified extracellular matrix [51], coexisting side--by-side with anchoring junctions, such as ectoplasmic specializations and desmosome-like junctions [52][53][54]. Sertoli cells and germ cells at different stages of differentiation are resting on the membrane, which plays a significant role in the spermatogenesis regulation and maintenance of the function and dynamic of the blood-testis barrier [52][53][54]. It can be supposed that the invaginations observed in the testes of experimental rats could affect the functions of the seminiferous epithelium caused by blood-testis barrier damage.…”

DHT deficiency perturbs the integrity of the rat seminiferous epithelium by disrupting tight and adherens junctions

“…However, the other proteins of adherens junctions studied by us display a somewhat contrary tendency. Because vinculin is considered as the regulator of the cadherin/catenin complex [6,15], we hypothesised that during the decline in cadherin and catenin expression, the increase of vinculin could be one of the protective mechanisms for preserving as well as possible the function of the SE in hormonal imbalance condition. However, this hypothesis needs more detailed examination.…”

“…In the basal ESs, b-catenin co-localizes with N-cadherin [14] and at the ESs site, vinculin, actin-binding protein is located. Vinculin, as a putative substrate for protein kinase, is involved in junction assembly, stabilization and regulation [6,15]; therefore vinculin is mentioned as a crucial regulator of the cadherin/ /catenin complex.…”

EXPRESSION OFβ-CATENIN IN HUMAN TESTES WITH SPERMATOGENIC DEFECTS

“…Adherens junctions (AJs) and desmosomes mediate cell-cell adhesion via members of the cadherin family of transmembrane proteins and their connections to the cortical actin-based cytoskeleton and the intermediate filament system that are established by catenins [5]. In rodent testes, unique actin-based AJs between Sertoli cells, as well as between Sertoli and germ cells, and intermediate filament-based desmosome-like junctions between Sertoli and germ cells, not only provide mechanical adhesion of germ cells onto Sertoli cells, they also play a crucial role in germ cell morphogenesis and differentiation [6,7,9,13]. To date, however, whether germ cells and Sertoli cells are equipped with this necessary AJ-associated signaling molecule to regulate spermatogenesis is not clear in human testis.…”