New insights into the pathological mechanism of varicocoele and its association with abnormal vascular remodeling in varicocoele patients

Abstract Background The pathological mechanism of venous reflux in varicocoele (VC) remains unclear. The theory of vascular remodeling may play an important role. Objective This study aims to explore the potential pathological mechanism of VC and its association with abnormal vascular remodeling in VC patients. Materials and Methods We collected specimens of spermatic veins from VC patients who received microsurgical varicocelectomies at the Department of Andrology, the Affiliated Hospital of Qingdao University, from January 2020 to January 2024. The spermatic veins of VC patients were divided into three subgroups based on diameter (<1 mm, 1–3 mm, and >3 mm), with a control group consisting of spermatic veins from hydrocele patients. Differences in venous morphology and ultrastructure between these groups were examined using optical microscopy (OM) and transmission electron microscopy (TEM). The expression of alpha‐smooth muscle actin (α‐SMA) and osteopontin (OPN) was evaluated by immunohistochemical staining and Western blot analysis. Results and Discussion Substantial hyperplasia and disordered arrangement of smooth muscle cells (SMCs) in the spermatic veins of VC patients were observed. Thickness and clumpy aggregation of collagen fibers were also noted under OM, with a significantly higher proportion observed. An increase in dense bodies and mitochondrial vacuolization in the VC group were revealed by TEM. Immunohistochemical staining showed that both α‐SMA and OPN were enriched in SMCs. Western blot analysis showed that the expression of OPN was significantly greater in the 1–3 mm and >3 mm subgroups compared with the control group ( p < 0.05), while the expression of α‐SMA did not show a significant decrease. Conclusions The pathological changes in morphology and overexpression of OPN in SMCs indicates a possible spermatic vascular transition from the contractile to secretory phenotype. This abnormal vascular remodeling might be associated with the reflux in the spermatic veins of VC patients.