H3K4me2 accompanies chromatin immaturity in human spermatozoa: an epigenetic marker for sperm quality assessment

Research Communication. et al.Chromatin remodeling, including histone post-translational modifications, during spermatogenesis can affect sperm quality and fertility, and epigenetic marks may therefore be useful for clinical evaluations of sperm. Together with histone hyperacetylation, the dimethylation of histone H3 on lysine K4 (H3K4me2) is also required during protamination. Accordingly, we evaluated the utilization of this epigenetic mark for the identification of sperm with decrease quality and immature chromatin. In this study, 99 semen samples, including 22 normozoospermic (N), 63 asthenozoospermic (A), and 14 oligoasthenozoospermic (OA) samples, were comprehensively analyzed with respect to H3K4me2 levels, DNA damage (DNA fragmentation index, DFI), and sperm immaturity (high DNA stainability, %HDS), as determined by a sperm chromatin structure assay using flow cytometry. We detected a significant relationship between H3K4me2 and %HDS (r = 0.47; p A > OA) indicates the importance of chromatin immaturity and histone code deviations in sperm evaluations. Using various approaches, our study elucidated H3K4me2 as a molecular marker of sperm quality with potential use in reproductive medicine.This work was supported by the University of Castilla-La Mancha and Junta de Comunidades de Castilla-La Mancha [SBPLY/17/180501/000470]; National Sustainability Programme I provided by the Ministry of Education, Youth and Sports of the Czech Republic [Nr. LO1503]; Ministry of Education, Youth and Sports of the Czech Republic [No. SVV 02690]; Charles University Research Fund [PROGRES Q39]; Ministry of Education, Youth and Sports of the Czech Republic and financed from The European Regional Development Fund [No. CZ.02.1.01/0.0/0.0/16_019/0000787 “Fighting]; University of Missouri [F21C program].Peer reviewe