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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

Cagri Camsari,1,3 Joseph K. Folger,1,3 Devin McGee,1,3 Steven J. Bursian,3 Hongbing Wang,4,5 Jason G. Knott,2,3 and George W. Smith1,3
Author Affiliations open
1Laboratory of Mammalian Reproductive Biology and Genomics, Michigan State University, East Lansing, Michigan 48824; 2Developmental Epigenetics Laboratory, Michigan State University, East Lansing, Michigan 48824; 3Department of Animal Science, Michigan State University, East Lansing, Michigan 48824; 4Department of Physiology, Michigan State University, East Lansing, Michigan 48824; 5Neuroscience Program, Michigan State University, East Lansing, Michigan 48824

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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.

  • This EHP Advance Publication article has been peer-reviewed, revised, and accepted for publication. EHP Advance Publication articles are completely citable using the DOI number assigned to the article. This document will be replaced with the copyedited and formatted version as soon as it is available. Through the DOI number used in the citation, you will be able to access this document at each stage of the publication process.

    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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