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Vocalization as a novel endpoint of atypical attachment behavior in 2,3,7,8-tetrachlorodibenzo-p-dioxin-exposed infant mice

  • Molecular Toxicology
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Abstract

Mammalian attachment behaviors, such as crying, are essential for infant survival by receiving food, protection, and warmth from caregivers. Ultrasonic vocalization (USV) of infant rodents functions to promote maternal proximity. Impaired USV emission has been reported in mouse models of autism spectrum disorder, suggesting that USV is associated with higher brain function. In utero and lactational dioxin exposure is known to induce higher brain function abnormalities in adulthood; however, whether perinatal dioxin exposure affects behavior during infancy is unclear. Therefore, we studied the impact of dioxin exposure on USV emission in infant mice born to dams treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 0.6 or 3.0 µg/kg) on gestational day 12.5. On postnatal days 3–9, USVs of the offspring were recorded for 1 min using a microphone in a sound-attenuated chamber. The total USV and mean call durations in infant mice exposed to 3.0 µg/kg, but not 0.6 µg/kg, were shorter than those in the control mice. In addition, the percentages of complicated call types (i.e., chevron and wave) in mice exposed to 3.0 µg/kg were decreased. Dioxin-induced gene expression changes occurred in the brains of mice exposed to 3.0 µg/kg; however, body weight, motor activity, and vocal fold structure were not significantly affected. These results suggest that infant USV is a useful behavioral endpoint in developmental neurotoxicity assessment that may be used to evaluate effects of chemical exposure on the infant–caregiver interaction.

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Acknowledgements

We are grateful to Ms. Junko Gorai and Dr. Masanobu Kohda for their excellent technical assistance. This work was supported in part by a grant from the JSPS Kakenhi (JP24221003 to C.T. and 17J07847 to E.K.).

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Authors and Affiliations

  1. Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Eiki Kimura & Chiharu Tohyama

  2. Center for Health and Environmental Risk Research, National Institute for Environmental Studies, Tsukuba, Japan

    Eiki Kimura

  3. Research Fellow of Japan Society for the Promotion of Science, Tokyo, Japan

    Eiki Kimura

  4. Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

    Chiharu Tohyama

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  1. Eiki Kimura
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Correspondence to Chiharu Tohyama.

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Kimura, E., Tohyama, C. Vocalization as a novel endpoint of atypical attachment behavior in 2,3,7,8-tetrachlorodibenzo-p-dioxin-exposed infant mice. Arch Toxicol 92, 1741–1749 (2018). https://doi.org/10.1007/s00204-018-2176-1

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