H3K4me2 accompanies chromatin immaturity in human spermatozoa: an epigenetic marker for sperm quality assessment
Language English Country Great Britain, England Media print-electronic
Document type Journal Article
- Keywords
- H3K4me2, Sperm DNA, chromatin immaturity, epigenetics, high DNA stainability,
- MeSH
- Semen Analysis MeSH
- Asthenozoospermia metabolism MeSH
- Biomarkers metabolism MeSH
- Adult MeSH
- Histone Code * MeSH
- Histones metabolism MeSH
- Humans MeSH
- Methylation MeSH
- Oligospermia metabolism MeSH
- Chromatin Assembly and Disassembly * MeSH
- Spermatozoa metabolism MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Biomarkers MeSH
- Histones MeSH
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 < 0.001). Furthermore, we observed negative correlations between H3K4me2 and sperm concentration, motility, and mitochondrial activity (p < 0.05). The increase in immaturity as semen quality decreased (N > 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.Abbreviations: A: asthenozoospermic; AO: acridine orange; ART: assisted reproductive therapy; BWW: Biggers-Whitten Whittingham; DAPI: 4',6' -diamidino-2-phenylindole; DFI: DNA fragmentation index; H3K4me2: dimethylation of lysine K4 on histones H3; HDS: high DNA stainability; HRP: horseradish peroxidase; MACS: magnetic-activated cell sorting; N: normospermic; NGS: normal goat serum; OA: oligoasthenozoospermic; PTM: post-translational modification; SCSA: sperm chromatin structure assay; SUTI: sperm ubiquitin tag assay; TBS-T: TBS with 0.5% Tween-20.
Biomedical Center in Pilsen Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic
Department of Gynecology and Obstetrics Charles University Pilsen Czech Republic
Department of Obstetrics Gynecology and Women's Health University of Missouri Columbia MO USA
Division of Animal Sciences University of Missouri Columbia MO USA
Genetika Plzeň s r o Pilsen Černice Czech Republic
References provided by Crossref.org
Nursing Exposure to Bisphenols as a Cause of Male Idiopathic Infertility
