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.