Rac Mediates Mouse Spermatogonial Stem Cell Homing to Germline Niches by Regulating Transmigration through the Blood-Testis Barrier

SummaryThe homing ability of spermatogonial stem cells (SSCs) allows them to migrate into niches after being transplantated into infertile testes. Transplanted SSCs attach to Sertoli cells and transmigrate through the blood-testis barrier (BTB), formed by inter-Sertoli tight junctions, toward niches on the basement membrane. The most critical step is the passage through the BTB, which limits the homing efficiency to <10%. Here we demonstrated the involvement of Rac1 in SSC transmigration. Rac1-deficient SSCs did not colonize the adult testes, but they reinitiated spermatogenesis when transplanted into pup testes without a BTB. Moreover, a dominant-negative Rac1 construct not only reduced the expression of several claudin proteins, which comprise the BTB, but also increased SSC proliferation both in vitro and in vivo. Short hairpin RNA (shRNA) -mediated suppression of claudin3, which was downregulated by Rac inhibition, reduced the SSC homing efficiency. Thus, Rac1 is a critical regulator of SSC homing and proliferation.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (278 K)Download as PowerPoint slideHighlights► Rac1 mediates spermatogonial stem cell homing to the niche by claudin regulation ► Rac1 plays an important role in transmigration through the blood-testis barrier ► Expression and activity of Rac1 are regulated by integrin and cytokine signals ► Rac1 regulates the proliferation of spermatogonial stem cells