The Mammalian Blood-Testis Barrier: Its Biology and Regulation

Abstract

Spermatogenesis is the cellular process by which spermatogonia develop into mature spermatids within seminiferous tubules, the functional unit of the mammalian testis, under the structural and nutritional support of Sertoli cells and the precise regulation of endocrine factors. As germ cells develop, they traverse the seminiferous epithelium, a process that involves restructuring of Sertoli-germ cell junctions, as well as Sertoli-Sertoli cell junctions at the blood-testis barrier. The blood-testis barrier, one of the tightest tissue barriers in the mammalian body, divides the seminiferous epithelium into 2 compartments, basal and adluminal. The blood-testis barrier is different from most other tissue barriers in that it is not only comprised of tight junctions. Instead, tight junctions coexist and cofunction with ectoplasmic specializations, desmosomes, and gap junctions to create a unique microenvironment for the completion of meiosis and the subsequent development of spermatids into spermatozoa via spermiogenesis. Studies from the past decade or so have identified the key structural, scaffolding, and signaling proteins of the blood-testis barrier. More recent studies have defined the regulatory mechanisms that underlie blood-testis barrier function. We review here the biology and regulation of the mammalian blood-testis barrier and highlight research areas that should be expanded in future studies.

Figure 1.

An electron micrograph of the intermediate compartment in the adult rat testis. This image shows 2 leptotene spermatocytes connected by intercellular bridges and enclosed within the intermediate compartment at stages IX–XI of the seminiferous epithelial cycle. The blood-testis barrier, which is created by Sertoli cells (SCs), is visible by the precipitation of lanthanum nitrate (arrowheads), which fails to advance beyond the TJs. Scale bar, 1 μm. (Reproduced from figure 1(e) of Mruk and Cheng [233] and used with permission.)

Figure 2.

An illustration of the different types of cell junctions in the seminiferous epithelium of the adult rat testis. There are 4 types of cell junctions in the testis: TJs, ectoplasmic specializations, desmosomes, and gap junctions.

Figure 3.

An electron micrograph of the blood-testis barrier in the adult rat testis. The blood-testis barrier is comprised of TJs, basal ectoplasmic specializations (ESs), desmosomes (DSs), and gap junctions (data not shown). TJs are typified by “kisses,” regions of contact between Sertoli cell plasma membranes (arrowheads). The basal ES is characterized by bundles of actin microfilaments (asterisks) positioned between the Sertoli cell plasma membrane and cisternae of endoplasmic reticulum (er). DSs are typified by electron dense material between Sertoli cells. Scale bar, 0.75 μm. (Reproduced from figure 4A of Sarkar et al [267] and used with permission).

Figure 4.

The localization of vimentin and γ-catenin in the adult rat testis. Testes were cryosectioned, fixed with methanol, and fluorescently immunostained for vimentin (green), a protein of the intermediate filament cytoskeleton, and γ-catenin (red), a protein of the desmosome and basal ectoplasmic specialization. This image shows a seminiferous tubule at stage IV of the seminiferous epithelial cycle. Vimentin localized to the Sertoli cell stalk, whereas plakoglobin localized at the blood-testis barrier. Cell nuclei were stained with 4′,6-diamidino-2-phenylindole. Scale bar, 10 μm.

Figure 5.

An illustration of the main proteins of the TJ, ectoplasmic specialization, desmosome, and gap junction at the blood-testis barrier in the adult rat testis.

Figure 6.

The localization of tubulin in the adult rat testis. Testes were fixed with Bouin's solution and embedded in paraffin wax. Tissue blocks were sectioned and immunostained for α-tubulin, a protein of the microtubule cytoskeleton. A–E, Seminiferous tubules at different stages of the seminiferous epithelial cycle. α-Tubulin localized at the blood-testis barrier (black arrowheads) (A), as well as to the luminal edge (blue arrowheads) (C and D), the Sertoli cell stalk (red arrowheads) (D), and the acrosome of late-step spermatids (green arrowheads) (E). There was no immunoreactive signal when the primary antibody was substituted with rabbit IgG (negative control) (F). The antibody was specific for α-tubulin when tested by immunoblotting (arrowhead) (G). The approximate positions of the molecular weight markers are shown to the left of the immunoblot. Scale bars, 50 μm (A–E) and 200 μm (F).