Regulation of the blood-testis barrier by a local axis in the testis: Role of laminin α2 in the basement membrane

Abstract

Lamininα2 is one of the constituent components of the basement membrane (BM) in adult rat testes. Earlier studies that used a mouse genetic model have shownthat a deletion of lamininα2 impedes male fertility by disrupting ectoplasmic specialization(ES; a testis-specific, actin-richanchoring junction) function along the length ofSertoli cell in the testis. This includes ES at the Sertoli cell-elongating/elongated spermatid interface, which is known as apical ES and possibly the Sertoli-Sertoli cell interface, known as basal ES, at the blood-testis barrier (BTB). Studies have also illustrated that there is a local regulatory axis that functionally links cellular events of spermiation that occur near the luminal edge of tubule lumen at the apical ES and the basal ES/BTB remodeling near the BMat opposite ends of the seminiferous epithelium during the epithelial cycle, knownas the apical ES-BTB-BM axis. However, theprecise role of BMin this axis remainsunknown.Here, we showthat lamininα2 intheBMserves as the crucial regulator inthis axis as laminin α2, likely its 80-kDa fragment from the C terminus, was found to be transported across the seminiferous epithelium at stagesVIII-IX of the epithelial cycle, from theBMto the luminal edge of the tubule, possibly being used to modulate apicalESrestructuring at these stages.Ofmore importance, aknockdownof lamininα2 inSertoli cells was shown to induce the Sertoli cell tight junction permeability barrier disruption via changes in localization of adhesion proteins at the tight junction and basal ES at the Sertoli cell BTB. These changes were found to be mediated by a disruption of F-actin organization that was induced by changes in the spatiotemporal expression of actin binding/regulatory proteins. Furthermore, laminin α2 knockdown also perturbed microtubule (MT) organization by considerable down-regulation of MT polymerization via changes in the spatiotemporal expression of EB1 (end-binding protein 1), a+TIP(MTplus-end tracking protein). Inshort, lamininα2 intheBMseems toplayacrucial role intheBTBBMaxis bymodulating BTB dynamics during spermatogenesis.-Gao, Y., Mruk, D., Chen, H., Lui, W.-Y., Lee, W. M., Cheng, C. Y. Regulation of the blood-testis barrier by a local axis in the testis: role of laminin α2 in the basement membrane. © FASEB.