Published date: Dec 12 2022

Journal Title: International Journal of Reproductive BioMedicine

Issue title: International Journal of Reproductive BioMedicine (IJRM): Volume 20, Issue No. 11

Pages: 941–954

DOI: 10.18502/ijrm.v20i11.12362

Anahid ShafieDepartment of Physiology, Faculty of Medicine, Tehran University of Medical Science, Tehran, Iran.

Farzaneh KianianDepartment of Physiology, Faculty of Medicine, Tehran University of Medical Science, Tehran, Iran.

Ghorbangol AshabiDepartment of Physiology, Faculty of Medicine, Tehran University of Medical Science, Tehran, Iran.

Mehri KadkhodaeeDepartment of Physiology, Faculty of Medicine, Tehran University of Medical Science, Tehran, Iran.

Mina RanjbaranDepartment of Physiology, Faculty of Medicine, Tehran University of Medical Science, Tehran, Iran.

Mahdi HajiaqaeiDepartment of Physiology, Faculty of Medicine, Tehran University of Medical Science, Tehran, Iran.

Keivan LorianResearch and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Arash AbdiDepartment of Physiology, Faculty of Medicine, Tehran University of Medical Science, Tehran, Iran.

Behjat Seifib-seifi@tums.ac.irDepartment of Physiology, Faculty of Medicine, Tehran University of Medical Science, Tehran, Iran.

Background: Despite the effectiveness of testosterone therapy in conditions associated with testosterone deficiency, including varicocele, several dose-dependent side effects limit the clinical use of testosterone therapy. Hydrogen sulfide, a toxic gas in high concentrations but a beneficial molecule in low concentrations, acts as both a major effector and an important inducer of testosterone.

Objective: This study investigated whether a subeffective dose of testosterone combined with a subeffective dose of hydrogen sulfide donor sodium hydrosulfide (NaHS) can be effective in an experimental varicocele model through a possible additive effect.

Materials and Methods: Thirty Wistar rats weighing 200-250 gr were divided into 5 groups as (n = 6/each): sham, varicocele, testosterone (200 μg/kg, 5 times per wk for 4 consecutive wk), NaHS (15 μmol/L, daily for 4 consecutive wk) and testosterone + NaHS (200 μg/kg, 5 times per wk + 15 μmol/L, daily, both for 4 consecutive wk). All animals, except in the sham group, underwent varicocele induction.

Results: The coadministration of testosterone and NaHS significantly increased serum testosterone (10.23 ± 0.95, p = 0.01), testicular H2S levels (608.94 ± 21.09, p < 0.001), and testicular superoxide dismutase activity (66.14 ± 1.56, p < 0.001), decreased malondialdehyde levels (0.77 ± 0.52, p < 0.001), and B-cell lymphoma 2-associated X protein to B-cell lymphoma 2 (0.16 ± 0.01, p < 0.001) protein expression ratio in the testicular tissues and improved sperm parameters and testicular histopathology compared to the varicocele group.

Conclusion: The combination therapy of subeffective doses of testosterone and NaHS can attenuate the varicocele-induced damages by reducing testicular oxidative stress and apoptosis and thus can be considered an effective approach with fewer side effects.

Key words: Apoptosis genes, Hydrogen sulfide, Oxidative stress, Sperm count, Testosterone, Varicocele.

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