| Alkylation of sperm DNA is associated with male factor infertility and a reduction in the proportion of oocytes fertilised during assisted reproduction. | |
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MedLine Citation:
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PMID: 20307685 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Approximately one-third of IVF cases in the UK are attributed to male factor infertility and in the majority of cases the origin of male infertility is unknown. The integrity of sperm DNA is important both for the success of assisted reproduction and the implications for the off-spring. One type of DNA damage that has not been investigated with respect to fertility outcomes is the adduct N7-methyldeoxyguanosine (N7-MedG), a biomarker for exposure to alkylating agents. A prospective cohort of couples attending for IVF had their N7-MedG levels in sperm measured using an immunoslot blot technique to examine whether sperm N7-MedG levels are associated with male factor infertility, semen quality measures or assisted reproduction outcomes. Sufficient DNA for analysis was obtained from 67/97 couples and N7-MedG was detected in 94% of sperm samples analysed. Men diagnosed with male factor infertility had significantly higher mean levels of N7-MedG in their sperm DNA (P=0.03). Logistic regression analysis showed that N7-MedG levels were significantly negatively associated with the proportion of oocytes successfully fertilised irrespective of the method of fertilisation used (IVF or intra-cytoplasmic sperm injection; ICSI, P<0.001). Therefore exposure to DNA alkylating agents is significantly associated with male infertility and the proportion of oocytes fertilised during assisted reproduction. Reducing such exposure may improve male fertility but further work is required to determine the relative importance of exogenous and endogenous sources of exposure. |
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Authors:
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S J Stocks; R M Agius; N Cooley; K L Harrison; D R Brison; G Horne; A Gibbs; A C Povey |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-03-20 |
Journal Detail:
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Title: Mutation research Volume: 698 ISSN: 0027-5107 ISO Abbreviation: Mutat. Res. Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-04-27 Completed Date: 2010-07-22 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0400763 Medline TA: Mutat Res Country: Netherlands |
Other Details:
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Languages: eng Pagination: 18-23 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier B.V. All rights reserved. |
Affiliation:
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Centre for Occupational and Environmental Health, School of Community-Based Medicine, Faculty of Medical and Human Sciences, University of Manchester, Oxford Rd, Manchester M13 9PL, UK. jillstocks@manchester.ac.uk |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Alkylating Agents / analysis DNA Adducts / analysis DNA Methylation* Deoxyguanosine / analogs & derivatives Female Guanine / analogs & derivatives, analysis Humans Infertility, Male / genetics* Male Middle Aged Reproductive Techniques, Assisted* Spermatozoa / ultrastructure* |
| Chemical | |
Reg. No./Substance:
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0/Alkylating Agents; 0/DNA Adducts; 28074-91-1/7-methyl-2-deoxyguanosine; 578-76-7/7-methylguanine; 73-40-5/Guanine; 961-07-9/Deoxyguanosine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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