Synergistic Effects of L-Carnitine and Moderate-Intensity Exercise on Testicular Damage Induced by Varicocele: Implications for miR-570, Irisin, Hsp70-2a, and Hsp90 Crosstalk.

Abstract

Objective: To study the effects of L-carnitine and moderate-intensity continuous exercise on varicocele-induced testicular damage, with emphasis on spermatogenesis, expression of stress-related proteins and microRNA, and hormonal changes in a rat model.

Design: Randomized, controlled laboratory animal study.

Subjects: Thirty-six adult male Wistar rats (200 ± 20 g) were randomly assigned to experimental groups.

Exposure: Animals were assigned to a sedentary control group, two untreated varicocele groups evaluated at 3 and 5 months, a varicocele group receiving oral L-carnitine (100 mg/kg) for 2 months, a varicocele group undergoing moderate-intensity continuous exercise, and a varicocele group receiving both treatments. Varicocele was induced surgically and confirmed by Doppler sonography and histopathological examination.

Main outcome measures: Testicular histopathology, expression levels of heat shock protein 70-2a, heat shock protein 90, and microRNA-570 assessed by molecular and immunohistochemical methods, and serum concentrations of testosterone and irisin.

Results: Varicocele induction resulted in vascular enlargement/congestion together with impaired dynamic testicular perfusion, degeneration of the germinal epithelium, and disrupted spermatogenesis. These alterations were accompanied by increased microRNA-570 expression and reduced heat shock protein 70-2a and heat shock protein 90 expression. L-carnitine and exercise improved testicular structure and spermatogenesis, reduced microRNA-570 expression, and restored heat shock protein levels, with the greatest overall improvement observed after the combined treatment. Serum testosterone and irisin concentrations increased after treatment; however, testosterone recovery was partial and did not exceed the level detected in the 3-month untreated varicocele group.

Conclusion: L-carnitine and moderate-intensity continuous exercise attenuated varicocele-induced testicular damage, with improvements in spermatogenesis accompanied by reduced miR-570 expression, restored Hsp70-2a/Hsp90 expression, and increased serum irisin and testosterone concentrations. The combined treatment produced the most consistent protective pattern; however, these preclinical findings do not establish causal relationships between the molecular or hormonal changes and testicular protection.