Abstract
Sperm DNA contains a range of DNA base damage that can arise, in part, from exposure to methylating agents. However, the effects are not fully characterized and so the aim of this study was to investigate associations between semen quality and the levels of N7-methyldeoxyguanosine (N7-MedG), a marker of exposure to methylating agents, and other markers of DNA damage and DNA methylation. Sperm samples were collected from 105 men attending an assisted reproduction clinic as part of a couple undergoing treatment for infertility and semen quality assessed manually according to WHO guidelines. Semen levels of N7-MedG, quantified by immunoslotblot, were significantly higher in men with sperm concentration < 15 × 106/ml (p ≤ 0.01), semen volume < 1.5 ml (p ≤ 0.05) and also in men with any aspect of semen quality below WHO reference levels (p ≤ 0.001). Measures of neutral Comet DNA damage were correlated with semen quality in a univariate analysis but not after adjustment for N7-MedG levels. Sperm concentration was negatively associated with % methylation at the gene for DAZL but no other marker of global or gene-specific DNA methylation. Results support the hypothesis that the known toxic and DNA damaging properties of alkylating agent exposure may have direct deleterious consequences on semen quality.
Highlights
Sperm DNA contains a range of DNA base damage that can arise, in part, from exposure to methylating agents
In this study of sperm DNA damage and DNA methylation of men attending for assisted reproduction treatment (ART) as part of a couple, the main finding was that N7-MedG levels were significantly associated with adverse semen quality even after adjustment for other markers of DNA damage as measured by the Comet assay
Measures of DNA damage assessed by the Comet assay were correlated with % progressive motility and % immotile sperm and differed in men whose semen quality was below WHO reference levels in a univariate analysis but not after adjustment for N7-MedG levels
Summary
Sperm DNA contains a range of DNA base damage that can arise, in part, from exposure to methylating agents. The effects are not fully characterized and so the aim of this study was to investigate associations between semen quality and the levels of N7-methyldeoxyguanosine (N7-MedG), a marker of exposure to methylating agents, and other markers of DNA damage and DNA methylation. The potential adverse consequences of exposure to DNA methylating and other alkylating agents on somatic cells i.e. toxicity, mutagenicity and carcinogenicity is well recognised[6]. We reported several years ago that N7-MedG levels, a biomarker of exposure to methylating agents[12], were associated with male factor infertility in a population of men attending as a part of a couple for ART5. The presence of N7-MedG in DNA, depending upon the type of alkylating agent exposure, may indicate significant levels of the pro-mutagenic, pro-carcinogenic and teratogenic adduct, O6-methylguanine[19]. To provide further information on these associations with semen quality, we have investigated these markers in sperm of men attending an infertility clinic as part of a couple
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
