Epigenetic role of miR-574 in sperm chromatin remodeling and developmental gene networks in male infertility

Context The epigenetic factors underlying varicocele and idiopathic infertility are still poorly understood, despite established pathophysiological mechanisms. Aims This study assessed sperm miR-574 expression in infertile males with or without varicocele and fertile controls, evaluating its relationship with semen parameters and chromatin condensation. Methods Thirty-eight participants were included, comprising idiopathic infertile men (n = 14), varicocele patients (n = 9), and fertile controls (n = 15). Aniline blue staining evaluated chromatin condensation; quantitative RT-PCR determined miR-574 expression. In silico analysis predicted target genes. Results Idiopathic infertile men exhibited significantly lower expression of sperm miR-574, indicated by significantly higher ΔCq levels, than fertile controls (P = 0.031). The idiopathic group also showed a significantly higher ratio of aniline blue-positive, histone-rich spermatozoa than the controls (P = 0.002). Across the entire study cohort, a significant negative correlation was established between miR-574 ΔCq levels and the proportion of spermatozoa with normal morphology (ρ = −0.465, P = 0.022). In silico analysis predicted that miR-574 targets key genes involved in chromatin regulation (H1FNT, CHD7), mitochondrial function (MRPS23, MARC2), and spermatogenesis (DAZL, SOHLH2). Conclusions These findings suggest a potential biological association where miR-574 downregulation may be a feature of idiopathic male infertility, potentially influencing gene networks involved in sperm formation and nuclear organization. Its precise regulatory mechanisms in male infertility subgroups warrant further large-scale validation. Implications Sperm miR-574 targets critical spermatogenesis and mitochondrial genes, representing a potential epigenetic factor involved in germ cell differentiation. Although its direct utility as a diagnostic biomarker requires further validation, it provides a valuable conceptual framework for understanding the molecular complexity of idiopathic male factor infertility.