title: Enhanced susceptibility of obese mice to glycidamide-induced sperm chromatin damage without increased oxidative stress.
abstract: 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.
authors: Division of Environmental Medicine, Department of Chemicals and Radiation, Norwegian Institute of Public Health, Oslo, Norway.
authors: K B
authors: KB
authors: Gutzkow
authors: Division of Environmental Medicine, Department of Chemicals and Radiation, Norwegian Institute of Public Health, Oslo, Norway.
authors: N
authors: N
authors: Duale
authors: Division of Environmental Medicine, Department of Chemicals and Radiation, Norwegian Institute of Public Health, Oslo, Norway.
authors: T
authors: T
authors: Danielsen
authors: Department of Environmental Science and Analytical Chemistry, Stockholm University, Stockholm, Sweden.
authors: H
authors: H
authors: von Stedingk
authors: Division of Environmental Medicine, Department of Chemicals and Radiation, Norwegian Institute of Public Health, Oslo, Norway.
authors: S
authors: S
authors: Shahzadi
authors: Division of Environmental Medicine, Department of Chemicals and Radiation, Norwegian Institute of Public Health, Oslo, Norway.
authors: C
authors: C
authors: Instanes
authors: Division of Environmental Medicine, Department of Chemicals and Radiation, Norwegian Institute of Public Health, Oslo, Norway.
authors: A-K
authors: AK
authors: Olsen
authors: Division of Environmental Medicine, Department of Food, Water and Cosmetics, Norwegian Institute of Public Health, Oslo, Norway.
authors: I-L
authors: IL
authors: Steffensen
authors: Division of Environmental Medicine, Department of Chemicals and Radiation, Norwegian Institute of Public Health, Oslo, Norway.
authors: T
authors: T
authors: Hofer
authors: Department of Environmental Science and Analytical Chemistry, Stockholm University, Stockholm, Sweden.
authors: M
authors: M
authors: Törnqvist
authors: Division of Environmental Medicine, Department of Chemicals and Radiation, Norwegian Institute of Public Health, Oslo, Norway.
authors: G
authors: G
authors: Brunborg
authors: Division of Environmental Medicine, Department of Chemicals and Radiation, Norwegian Institute of Public Health, Oslo, Norway.
authors: B
authors: B
authors: Lindeman
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D053938:DNA Fragmentation / Q000187:drug effects; D059305:Diet, High-Fat; D004852:Epoxy Compounds / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009765:Obesity / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism*; D013737:Testis / Q000187:drug effects / Q000378:metabolism
chemical_list: D002843:Chromatin; D004852:Epoxy Compounds; C071834:glycidamide
keywords: DNA damage; gene expression; glycidamide; obesity; oxidative stress; sperm chromatin integrity