Spatially Heterogeneous Impairment of Spermatogenesis in the Testis Following Efferent Duct Transection in Mice

Obstructive azoospermia, with a sustained elevation in intratesticular pressure, leads to seminiferous epithelium degeneration. However, studies using efferent duct ligation have not fully elucidated the chronic changes in the testis caused by obstruction.

Using the efferent duct transection model, we aimed to elucidate the temporal and spatial progression of spermatogenic impairment in the mouse testis.

Male mice underwent efferent duct transection and were analyzed at five time points up to 20 weeks. A three-dimensional reconstruction of serial testis sections was employed to visualize and quantitate impaired spermatogenesis in the seminiferous tubules.

The volumes of the testis, seminiferous tubules, and interstitium showed 2-3-fold increases 1 week post-transection, but normalized by 5 weeks. The volume of the rete testis continued to increase, and was 9.3-fold larger by 20 weeks. The impairment of spermatogenesis in the seminiferous epithelium was progressive until 20 weeks. Three-dimensional mapping revealed marked spatial heterogeneity in impaired spermatogenesis: cranial seminiferous tubules remained highly viable, while the majority of caudal tubules were impaired. Furthermore, areas of severe impairment were identified in tubule regions near the rete testis in all tubules.

The present results suggest that chronic obstructive stress, driven by mechanical stress and/or local ischemia, is dominant in the caudal region and near the rete testis of the mouse testis. This study established a crucial link between obstructive azoospermia and a pathology resembling non-obstructive azoospermia, underscoring the importance of evaluating such spatial vulnerability in the clinical management of obstructive male infertility.