Population Variability and the Teratogenic Effects of Dioxin During Pregnancy

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2019-04-15

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Abstract

Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) during pregnancy is of particular concern as it interrupts fetal growth and development. While susceptibility to many toxicants often varies among individuals due to genetic differences, current studies of the teratogenic effects of dioxin do not account for inter-individual variability when evaluating exposure risks. Our study aims to evaluate the effects of dioxin exposure on pregnant females and fetal development in genetically diverse mice to determine how genetic background impacts susceptibility. We developed an in vivo study with a panel of mice that collectively mimic a heterogeneous human population. In this study, pregnant female mice from 16 diverse mouse strains are exposed to one of three doses of dioxin (0, 1, 100 ng/kg/day) for a period of 10 days following mating. At E10.5 (post-mating) mice are euthanized and embryos dissected. To determine effects of dioxin at different doses, non-cancerous pregnancy-related and cardiogenic endpoints were assessed. We found that genetic background influences response variation in both a strain- and endpoint-dependent manner. This data emphasizes the importance of accounting for genetic background when studying the effects of toxic chemical compounds and individual susceptibility.

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Dioxin, TCDD, Embryogenesis, Cardiogenesis

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