Sperm tRNA-Derived Fragment-36 Expression in Varicocele: Associations with Disease Severity, Semen Parameters and Reproductive Hormones.

Abstract

Varicocele is a prevalent and potentially reversible cause of male infertility; however, the molecular mechanisms underlying its pathogenesis remain poorly understood. Transfer RNA-derived fragments (tRFs) have emerged as important regulators of reproductive and vascular dysfunction, yet their role in varicocele has not been explored. This study aimed to evaluate the expression of tRF-23, tRF-36 and tRF-40 in spermatozoa from men with varicocele and healthy controls, and to determine whether their expression is associated with reproductive hormone levels and semen quality. Blood and semen samples were collected from 60 patients with clinically graded varicocele (n = 20 per grade) and 20 controls. Expression levels of tRFs were quantified using qRT-PCR. All three tRFs were detected in spermatozoa from both patients and controls. Relative to controls, tRF-23 and tRF-36 expression levels were increased by 1.23-fold and 1.52-fold, respectively, whereas tRF-40 expression was reduced to 0.9-fold; however, these differences did not reach statistical significance (p > 0.05). Stratification by varicocele grade revealed a distinct expression pattern for tRF-36, which was significantly downregulated in grade III compared with grade I varicocele patients (4.52-fold decrease, p = 0.010). Correlation analyses demonstrated significant associations among the three tRFs, and all were negatively correlated with sperm concentration. Collectively, these findings provide the first evidence linking tRF expression to varicocele and suggest a potential role for tRFs in the molecular pathology of this condition.