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Junction interaction in the seminiferous epithelium: regulatory roles of connexin-based gap junction.

Anchoring junction, tight junction (TJ), and gap junction (GJ) constitute three major junction types in mammalian testes. Connexin is the well-studied GJ protein. It forms the building block of connexon, which is composed of six connexin units. Connexon forms the functional GJ when pairing with counter-connexon from neighboring cells. In the testis, at least eleven connexins are associated with the Sertoli and germ cells of the seminiferous epithelium and the Leydig cells of the interstitium, modulating spermatogenesis and steroidogenesis, respectively. Significantly, connexins are recently speculated to act as regulators of other junctions in the testes using pan-connexin peptide model. This demonstrates that the loss of connexin function leads to a preferential degradation of occludin-based TJ, but not N-cadherin-based adherens junction (AJ), in the testis, despite the intermingled relationship of these three junctions at the site of blood-testis barrier. In the clinical aspects, connexins are shown to relate to male infertility and testicular dysfunctions. A panel of molecules and proteins and their associated protein kinases are actively participating in the regulation of connexin-mediated GJ and fine-tuning connexin-associated functions in the testis. Herein, we summarize the latest findings of connexins in the testis in the aspects of fertility, and testicular diseases, with emphasis on the unexplored roles of connexins in regulating other junction types. This can shed light on future studies in implicating the putative roles of connexins in the physiological functions of reproduction and the clinical aspects of male infertility. In addition, understanding the roles of connexins can advance the diagnosis and treatment of testicular dysfunction and infertility.