Research Articles Advance Publication
Environ Health Perspect; DOI:10.1289/EHP481
Effects of Periconception Cadmium and Mercury Co-Administration to Mice on Indices of Chronic Disease in Male Offspring at Maturity
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Background: Long-term exposure to the heavy metals cadmium (Cd) and mercury (Hg) is known to increase risk of chronic diseases. However, to our knowledge, exposure to Cd and Hg beginning at the periconception period has not been studied to date.
Objective: The effect of co-administration of Cd and Hg during early development on indices of chronic diseases at adulthood was examined.
Methods: Adult female CD1 mice were subcutaneously administered a combination of cadmium chloride (CdCl2) and methylmercury (II) chloride (CH3HgCl; 0, 0.125, 0.5 or 2.0 mg/kg body weight each) four days before and four days after conception (8 days total). Indices of anxiety-like behavior, glucose homeostasis, endocrine and molecular markers of insulin resistance and organ weights were examined in adult male offspring.
Results: Increased anxiety-like behavior, impaired glucose homeostasis, and higher body weight and abdominal adipose tissue weight were observed in male offspring of treated females compared to controls. Significantly increased serum leptin and insulin concentrations and impaired insulin tolerance in the male offspring of dams treated with 2.0 mg/kg body weight of Cd and Hg suggested insulin resistance. Altered mRNA abundance for genes associated with glucose and lipid homeostasis (GLUT4, IRS1, FASN, ACACA, FATP2, CD36, G6PC) in liver and abdominal adipose tissues as well as increased IRS1 phosphorylation in liver (Ser 307) provided further evidence of insulin resistance.
Conclusions: Results suggest administration of cadmium and mercury to female mice during early development of their offspring (which in this study is the periconception period) was associated with anxiety-like behavior, altered glucose metabolism and insulin resistance in male offspring at adulthood.
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Citation: Camsari C, Folger JK, McGee D, Bursian SJ, Wang H, Knott JG, Smith GW. Effects of Periconception Cadmium and Mercury Co-Administration to Mice on Indices of Chronic Disease in Male Offspring at Maturity. Environ Health Perspect; http://dx.doi.org/10.1289/EHP481
Received: 9 May 2016
Revised: 17 October 2016
Accepted: 18 October 2016
Published: 4 November 2016
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