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PMID: 19696015 Published · ppublish English Journal Article Research Support, N.I.H., Intramural

Diet-induced obesity in male mice is associated with reduced fertility and potentiation of acrylamide-induced reproductive toxicity.

Biology of reproduction ·Vol. 82 ·No. 1 ·2010-01-00 ·Pages 96-104

Ghanayem BI, Bai R, Kissling GE, Travlos G, Hoffler U

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.

MeSH Terms
Acrylamide/toxicity Adipose Tissue Animals Blood Glucose/metabolism Body Weight Cholesterol/blood Copulation Cytochrome P-450 CYP2E1/drug effects Dietary Fats/adverse effects Female Germ-Line Mutation/drug effects Infertility, Male/chemically induced Insulin/blood Leptin/blood Male Mice Mice, Inbred C57BL Obesity/complications,metabolism Paternal Exposure Pregnancy Pregnancy Rate Reverse Transcriptase Polymerase Chain Reaction Sperm Count Sperm Motility Testis/metabolism Triglycerides/blood
Chemicals
Blood Glucose Dietary Fats Insulin Leptin Triglycerides Acrylamide Cholesterol Cytochrome P-450 CYP2E1
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Ghanayem Burhan I
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
Bai Re
Kissling Grace E
Travlos Greg
Hoffler Undi
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Article Info
Journal
Biology of reproduction
Abbr.
Biol Reprod
ISSN
1529-7268
DOI
10.1095/biolreprod.109.078915
Email
ghanayem@niehs.nih.gov
Published
2010-01-00
Epub
2009-00-19
Pages
96-104
Language
English
Region
United States
NLM ID
0207224
PMCID
PMC2802115
Subset
IM
Grants
Intramural NIH HHS · United States
Corrections
CommentIn
PMID: 19906686
External Links
PubMed source DOI: 10.1095/biolreprod.109.078915 PMC Full Text View journal details
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