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

Biol Reprod. 2010 Jan;82(1):96-104. doi: 10.1095/biolreprod.109.078915. Epub 2009 Aug 19.


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.

Publication types

  • Research Support, N.I.H., Intramural

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*
  • Obesity / metabolism
  • Paternal Exposure*
  • Pregnancy
  • Pregnancy Rate
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sperm Count
  • Sperm Motility
  • Testis / metabolism
  • Triglycerides / blood


  • Blood Glucose
  • Dietary Fats
  • Insulin
  • Leptin
  • Triglycerides
  • Acrylamide
  • Cholesterol
  • Cytochrome P-450 CYP2E1