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


Hekim N., Gunes S., Asci R.

REPRODUCTION FERTILITY AND DEVELOPMENT, cilt.38, sa.15, 2026 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 38 Sayı: 15
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1071/rd26110
  • Dergi Adı: REPRODUCTION FERTILITY AND DEVELOPMENT
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, MEDLINE, Zoological Record, Academic Search Ultimate (EBSCO)
  • Anahtar Kelimeler: aniline blue, epigenetic, histone, idiopathic male infertility, miR-574, sperm chromatin condensation, sperm epigenetics, varicocele
  • Ondokuz Mayıs Üniversitesi Adresli: Evet

Özet

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 Delta Cq 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 Delta Cq levels and the proportion of spermatozoa with normal morphology (rho = -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.