The blood-testis barrier: Its biology, regulation, and physiological role in spermatogenesis

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The blood-testis barrier (BTB) in mammals, such as rats, is composed of the tight junction (TJ), the basal ectoplasmic specialization (basal ES), the basal tubulobulbar complex (basal TBC) (both are testis-specific actin-based adherens junction [AJ] types), and the desmosome-like junction that are present side-by-side in the seminiferous epithelium. The BTB physically divides the seminiferous epithelium into basal and apical (or adluminal) compartments, and is pivotal to spermatogenesis. Besides its function as an immunological barrier to segregate the postmeiotic germ-cell antigens from the systemic circulation, it creates a unique microenvironment for germ-cell development and confers cell polarity. During spermatogenesis, the BTB in rodents must physically disassemble to permit the passage of preleptotene and leptotene spermatocytes. This occurs at late stage VII through early stage VIII of the epithelial cycle. Studies have shown that this dynamic BTB restructuring to facilitate germ-cell migration is regulated by two cytokines, namely transforming growth factor-β3 (TGF-β3) and tumor necrosis factor-α (TNFα), via downstream mitogen-activated protein kinases. These cytokines determine the homeostasis of TJ- and basal ES-structural proteins, proteases, protease inhibitors, and other extracellular matrix (ECM) proteins (e.g., collagen) in the seminiferous epithelium. Some of these molecules are known regulators of focal contacts between the ECM and other actively migrating cells, such as macrophages, fibroblasts, or malignant cells. These findings also illustrate that cell-cell junction restructuring at the BTB is regulated by mechanisms involved in the junction turnover at the cell-matrix interface. This review critically discusses these latest findings in the field in light of their significance in the biology and regulation of the BTB pertinent to spermatogenesis.