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Enhanced susceptibility of obese mice to glycidamide-induced sperm chromatin damage without increased oxidative stress
Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
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Number of Authors: 12
2016 (English)In: Andrology, ISSN 2047-2919, E-ISSN 2047-2927, Vol. 4, no 6, 1092-1114 p.Article in journal (Refereed) Published
Abstract [en]

Diet-induced obesity is known to impair male reproduction and may aggravate the male reproductive toxicity of the food contaminant acrylamide. Exposure of male mice to acrylamide induces paternally mediated pre- and post-implantation losses because of spermatozoal toxicity and these effects are potentiated in mice fed a high-fat diet. Glycidamide - an acrylamide metabolite - is the primary mediator of reproductive effects in males. The mechanisms causing the interaction between diet and acrylamide are not clear. However, diet-induced obesity is associated with oxidative stress in male reproductive tissues which might contribute to increased germ cell susceptibility. In this study, we investigated whether a moderate diet-induced obesity regimen could interfere with glycidamide-induced spermatozoal toxicity and increase oxidative stress. For this purpose, sperm chromatin integrity, oxidised DNA and protein levels, transcript levels of oxidative stress responsive genes and glycidamide-induced DNA and haemoglobin adducts were analysed in samples from male mice exposed to a high-fat diet for 6 weeks in combination with a single glycidamide exposure 7 days prior to sacrifice. We found that glycidamide-induced sperm DNA fragmentation was markedly higher in obese than in lean mice. However, the levels of oxidised DNA and/or protein in blood, liver and testicular tissue was lower in obese than in lean mice. Accompanying the reduced level of oxidised macromolecules, the transcript levels of several oxidative stress-related genes were altered in the liver and testis from obese mice suggesting induction of an antioxidant response in these animals. The haemoglobin-glycidamide adduct levels were higher in obese than in lean animals, whereas obesity did not seem to increase the level of glycidamide-induced DNA adducts. These findings show that a moderate diet-induced obesity regimen may potentiate glycidamide-induced sperm cells toxicity and suggest that the increase in glycidamide-induced sperm toxicity observed in obese mice does not depend on overt oxidative stress.

Place, publisher, year, edition, pages
2016. Vol. 4, no 6, 1092-1114 p.
Keyword [en]
DNA damage, gene expression, glycidamide, obesity, oxidative stress, sperm chromatin integrity
National Category
Obstetrics, Gynecology and Reproductive Medicine Biological Sciences
Identifiers
URN: urn:nbn:se:su:diva-144569DOI: 10.1111/andr.12233ISI: 000401696200014PubMedID: 27575329OAI: oai:DiVA.org:su-144569DiVA: diva2:1114960
Available from: 2017-06-26 Created: 2017-06-26 Last updated: 2017-06-26Bibliographically approved

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