Varicocele is a common disease of the male reproductive system and is the main cause of male infertility; however, the pathological mechanisms of varicocele remain unclear. The anchoring junctions (AJs) in the testies are located between Sertoli cells, or between Sertoli cells and germ cells. Intact and functional AJs are crucial for spermatogenesis. In the present study, the histomorphology, ultrastructure of AJ, cell cycle, expression of AJ structural proteins, and the level of AJ-associated signaling molecules were investigated in the left testes of experimental varicocele rats at 8 and 12 weeks after surgery. The results revealed that varicocele induced the loss of premature germ cells from the seminiferous epithelium. Furthermore, the results of the present study also revealed damage to the AJ ultrastructure, disorientation of the spermatid head, deregulation of the cell cycle, downregulation of AJ structural proteins, enhanced phosphorylation of focal adhesion kinase (FAK) at Tyr397 and its downstream adapter Src at Tyr416, and activation of the extracellular signal-regulated protein kinase 1 (ERK1) signaling pathway. Thus, the present study demonstrated that varicocele disrupted the structure and function of AJs in the left testes of rats, and that enhancement of FAK phosphorylation may contribute to AJ damage by activating ERK1 signaling, disrupting actin-based filament networks, and altering the balance of the apical ectoplasmic specialization-blood testis barrier functional axis. These findings provide important insights into the pathological mechanisms through which varicocele contributes to male infertility and could help to identify new therapeutic targets for varicocele.
Keywords: anchoring junction; phosphorylated focal adhesion kinases; varicocele.
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