title: Diet-induced obesity in male mice is associated with reduced fertility and potentiation of acrylamide-induced reproductive toxicity.
abstract: The prevalence of human obesity and related chronic disorders such as diabetes, cardiovascular diseases, and cancer is rapidly increasing. Human studies have shown a direct relationship between obesity and infertility. The objective of the current work was to examine the effect of diet-induced obesity on male fertility and the effect of obesity on susceptibility to chemical-induced reproductive toxicity. From 5 to 30 wk of age, genetically intact male C57Bl/6J mice were fed a normal diet or one in which 60% of the kilocalories were from lard. Obese mice exhibited significant differences in the mRNA of several genes within the testes in comparison to lean males. Pparg was increased 2.2-fold, whereas Crem, Sh2b1, Dhh, Igf1, and Lepr were decreased 6.7, 1.4, 3.2, 1.6, and 7.2-fold, respectively. The fertility of male mice was compared through mating with control females. Acrylamide (AA)-induced reproductive toxicity was assessed in obese or lean males treated with water or 25 mg AA kg(-1) day(-1) via gavage for 5 days and then mated to control females. Percent body fat and weight were significantly increased in mice fed a high-fat vs. a normal diet. Obesity resulted in significant reduction in plugs and pregnancies of control females partnered with obese vs. lean males. Serum leptin and insulin levels were each approximately 5-fold higher in obese vs. age-matched lean mice. Sperm from obese males exhibited decreased motility and reduced hyperactivated progression vs. lean mice. Treatment with AA exacerbated male infertility of obese and lean mice; however, this effect was more pronounced in obese mice. Further, females partnered with AA-treated obese mice exhibited a further decrease in the percentage of live fetuses, whereas the percentage of resorptions increased. This work demonstrated that diet-induced obesity in mice caused a significant reduction in male fertility and exacerbated AA-induced reproductive toxicity and germ cell mutagenicity.
authors.affiliation: Laboratory of Pharmacology, Biostatistics Branch, and Cellular and Molecular Pathology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. ghanayem@niehs.nih.gov
authors.forename: Burhan I
authors.initials: BI
authors.lastname: Ghanayem
authors.forename: Re
authors.initials: R
authors.lastname: Bai
authors.forename: Grace E
authors.initials: GE
authors.lastname: Kissling
authors.forename: Greg
authors.initials: G
authors.lastname: Travlos
authors.forename: Undi
authors.initials: U
authors.lastname: Hoffler
mesh_terms: D020106:Acrylamide / Q000633:toxicity*; D000273:Adipose Tissue; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D003307:Copulation; D019392:Cytochrome P-450 CYP2E1 / Q000187:drug effects*; D004041:Dietary Fats / Q000009:adverse effects; D005260:Female; D018095:Germ-Line Mutation / Q000187:drug effects*; D007248:Infertility, Male / Q000139:chemically induced*; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications* / Q000378:metabolism; D018812:Paternal Exposure; D011247:Pregnancy; D018873:Pregnancy Rate; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013076:Sperm Count; D013081:Sperm Motility; D013737:Testis / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D020738:Leptin; D014280:Triglycerides; D020106:Acrylamide; D002784:Cholesterol; D019392:Cytochrome P-450 CYP2E1
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