Age-dependent morphological, morphometric and Ki-67 proliferative changes in the rat testis under experimental chronic renal failure and their correction with Ferula moschata (sumbul) root.

BACKGROUND

Chronic renal failure (CRF), the advanced stage of chronic kidney disease (CKD), is a systemic disorder that affects extrarenal organs, including the male gonads, yet the age-related dynamics of testicular structural injury and its pharmacological correction remain insufficiently characterised. We evaluated age-dependent morphological, morphometric and proliferative (Ki-67) alterations of the testis in an experimental model of CRF and assessed the corrective potential of an infusion of Ferula moschata (sumbul) root, a plant used in regional traditional medicine and reported to possess antioxidant and anti-inflammatory activity.

METHODS

The study was performed at Bukhara State Medical Institute (2023-2025) on 140 outbred male white rats aged 3, 6 and 9 months, allocated to three groups: intact control (Group I, n = 40); CRF induced by the Greven glycerol method (Group II, n = 50); and CRF followed by one month of oral Ferula moschata root infusion (Group III, n = 50). CRF was confirmed biochemically (serum urea and creatinine) and by renal histology. Testes were assessed by organometry, light microscopy (haematoxylin-eosin, H&E, and van Gieson staining), quantitative morphometry (tunica albuginea thickness, seminiferous tubule diameter and cross-sectional area, germinal epithelium thickness, tubular lumen diameter) and Ki-67 immunohistochemistry (IHC) with digital quantification (QuPath 0.5.0, ×200). Data (M ± m) were analysed after Kolmogorov-Smirnov normality testing using the two-sample Student t-test and the Mann-Whitney U-test, with significance at p ≤ 0.05.

RESULTS

CRF produced progressive, age-amplified testicular injury. Relative to age-matched controls, seminiferous tubule diameter fell from 178.1 ± 1.04-151.62 ± 1.84 µm at 6 months and from 163.2 ± 1.1-140.34 ± 2.19 µm at 9 months, tubule cross-sectional area and germinal epithelium thickness decreased, and the tunica albuginea thickened; the germinal epithelium thinned by 8.1% at 3 months, 25.5% at 6 months and ∼30% at 9 months. Ki-67 proliferative expression, which physiologically peaked at 6 months in controls (35.9%, 44.23% and 23.2% at 3, 6 and 9 months), fell markedly under CRF (18.1%, 10.74% and 2.94%; 3-8-fold lower than control). One month of Ferula moschata correction partially restored the morphometric indices (e.g., 6-month tubule diameter to 160.29 ± 2.24 µm) and increased Ki-67 expression (25.12%, 32.9% and 12.1%; 2-6-fold higher than CRF), approaching control values. Recovery was greatest in younger animals and least in 9-month-old rats.

CONCLUSION

Experimental CRF induces age-dependent structural degeneration and suppressed proliferative activity in the rat testis, which are partially reversible by Ferula moschata root infusion, most effectively when treatment begins at a younger age. Ki-67 is a reliable marker of the CRF-related decline in testicular proliferation, and Ferula moschata root merits further study as an adjuvant gonadoprotective phytotherapeutic.