Alterations Expression of Key RNA Methylation (m6A) Enzymes in Testicular Tissue of Rats with Induced Varicocele

Epigenetics impacts male fertility and reproductive disorders. RNA modifications, like m6A, influence RNA metabolism. Varicocele contributes to male infertility, and oxidative stress affects sperm function. This study investigates the expression of key RNA modification enzymes in a rat varicocele model, aiming to elucidate the relationship between varicocele, oxidative stress, and fertility. Fifteen male Wistar rats were divided into Control, Sham, and Varicocele induction groups. Varicocele was induced in the rats surgically. After 8 weeks, testicular tissues and sperm were collected for analysis, including histopathological assessment and evaluation of sperm parameters, functional tests, and gene expression of key RNA modification enzymes: METTL3 as a writer, ALKBH5 and FTO as erasers, and YTHDF2 as a reader involved in recognizing m6A-modified RNA using qRT-PCR. One-way ANOVA with post-hoc Tukey HSD was used for comparing tests within groups. Varicocele induction resulted in histological changes in testicular tissues, including irregularly variable-sized seminiferous tubules. Sperm parameters were significantly affected, with lower concentration, motility, and higher percentage of abnormal sperm in the varicocele group. Increased levels of oxidative stress markers (Sperm lipid peroxidation, and intracytoplasmic ROS) and sperm DNA damage were observed, indicating the presence of oxidative stress in varicocele. Moreover, the expression of key enzymes involved in RNA metabolism was downregulated in the varicocele group. These findings highlight the detrimental impact of varicocele on testicular health, sperm quality, and gene expression, providing insights into the underlying mechanisms of male infertility associated with varicocele.