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J Appl Toxicol. 2014 Mar;34(3):296-306. doi: 10.1002/jat.2881. Epub 2013 Jun 10.

In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin modulates dysregulation of the lipid metabolism in mouse offspring fed a high-calorie diet.

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Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Bunkyo-ku, Tokyo, 113-0033, Japan.


Exposure to environmental chemicals, including dioxins, is a risk factor for type 2 diabetes mellitus in humans. This study explored the hypothesis that in utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic congener among dioxins, aggravates this disease state later in adulthood. Pregnant C57Bl/6 J mice were administered either a single oral dose of TCDD (3.0 µg kg(-1) body weight) or corn oil on gestational day 12.5. The male pups born to these two groups of dams were given either a regular diet or a high-calorie diet, after postnatal day (PND) 28. The four groups of investigated offspring were thus termed T-R (TCDD regular diet), T-H (TCDD high-calorie diet), V-R (vehicle regular diet), and V-H (vehicle high-calorie diet). The mice were regularly monitored for body weight, blood pressure and glucose, until they reached 26 weeks of age. Mice in the V-H group were significantly obese at weeks 15 and 26, but they exhibited no diabetes-associated signs of insulin resistance or hypertension. However, metabolic syndrome-related alterations with marginal signs of liver damage were found at week 26. Pronounced signs of dysregulated lipid metabolism with altered gene expression and liver inflammation were already present at week 15, whereas such alterations were suppressed in the T-H group. Although the mechanism is unclear, this study showed that in utero and lactational exposure to low-dose TCDD does not aggravate obesity-induced disease states, such as adult-onset diabetes, but instead attenuates the dysregulation of lipid metabolism brought on by a high-calorie diet.


dioxin; environmental chemicals; glucose and lipid metabolism; maternal exposure; mouse

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