Effect of Rho Kinase Inhibitor (Y27632) on Spermatogenesis in Azoospermic Mice Model.

Authors

Sara Bolboleh, Tahmineh Peirouvi, Sina Karimipour, Neda Abedpour, Tohid Rezaei Topraggaleh

Published in

Reproductive sciences (Thousand Oaks, Calif.). Oct 23, 2026. Epub Oct 23, 2026.

Abstract

Advances in cancer therapy have markedly improved patient survival, thereby increasing the need for effective fertility preservation strategies. Chemotherapeutic agents commonly induce apoptosis in rapidly proliferating cells, including spermatogonia, resulting in long-term testicular damage. Y-27632, a Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitor, has been shown to suppress apoptosis in various stem cell populations by modulating Rho GTPase-dependent signaling pathways. This study aimed to evaluate the protective effects of Y-27632 against busulfan-induced testicular injury in a murine model. Eighteen 4-week-old male C57BL/6 mice were randomly assigned to three groups: control (no treatment), busulfan (40 mg/kg), and busulfan plus Y-27632 (40 mg/kg busulfan + 5 mg/kg Y-27632). Seventy days after treatment, sperm parameters (count, motility, viability, and plasma membrane integrity) and testicular outcomes, including seminiferous tubule diameter, germinal epithelium thickness, tubular differentiation index, spermatogenesis index, Johnsen score, apoptotic gene expression, malondialdehyde levels, total antioxidant capacity, and TUNEL-positive cells, were assessed. Y-27632 administration significantly improved seminiferous tubule diameter and germinal epithelium thickness and increased tubular differentiation and spermatogenesis indices and Johnsen scores compared with the busulfan group. In addition, Y-27632 treatment was associated with reduced ERK gene expression and a lower number of TUNEL-positive cells. However, sperm parameters and testicular weight remained significantly reduced compared with controls, and no significant differences were observed in lipid peroxidation, total antioxidant capacity, or sperm DNA integrity among groups. In conclusion, Y-27632 partially attenuated busulfan-induced testicular damage by improving histological indices of spermatogenesis and reducing apoptosis, suggesting that ROCK inhibition may represent a potential adjunct strategy for fertility preservation following gonadotoxic cancer therapies.

PMID:
42920066
Bibliographic data and abstract were imported from PubMed on 24 Oct 2026.

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