Injury and recovery patterns of the blood-testis barrier and spermatogenic function in a surgical unilateral cryptorchidism model in rats

BACKGROUND: Cryptorchidism is one of the most common congenital disorders of the pediatric urogenital system. In addition to regulating the passage of substances into and out of the seminiferous epithelium, the blood-testis barrier (BTB) plays a critical role in maintaining a stable microenvironment for spermatogenesis. BTB alterations in cryptorchidism remain poorly characterized. This study aimed to establish a surgical unilateral cryptorchidism model in rats (SUCMR) and to investigate the injury and recovery patterns of both the BTB and spermatogenic function within this model. METHODS: The SUCMR was performed on 6-week-old male Sprague-Dawley rats, and testicular changes were observed after maintaining the modeling state for multiple time points. Simultaneously, another batch of rats underwent testicular descent surgery after maintaining the modeling for different durations to observe testicular recovery. The testis mass and volume, epididymal mass, epididymal sperm count and sperm malformation rate were quantified. After HE staining of testicular tissue, the seminiferous tubule structure was observed, and the seminiferous tubule diameter and seminiferous epithelium thickness were statistically analyzed. Biotin tracing experiments and transmission electron microscopy were performed to detect the BTB integrity. The expression of key BTB proteins ZO-1, OCCLUDIN, and CLAUDIN-11 was detected by WB. According to the normality of data distribution, a paired t-test or the Wilcoxon signed-rank test, an unpaired t-test or the Mann-Whitney U test, a one-way analysis of variance (ANOVA) or the Kruskal-Wallis test were used. A p-value of less than 0.05 was considered statistically significant. RESULTS: In SUCMR, sloughing of the seminiferous epithelium was observed, resulting in testicular atrophy and spermatogenic abnormalities. The SUCMR impaired the integrity of the BTB and leaded to a progressive decrease in the expression of the key barrier proteins. Testicular atrophy and spermatogenic function injury induced by short-term SUCMR were reversible. But the disruption to the BTB was irreversible when the SUCMR was maintained for 4 weeks or longer. CONCLUSION: In this model, spermatogenic dysfunction and BTB injury progressed with increasing duration of abdominal retention, and abnormalities induced by 4 or 6 weeks of SUCMR did not recover within the post-orchiopexy observation period.