Archives of Toxicology

, Volume 92, Issue 5, pp 1741–1749 | Cite as

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

  • Eiki Kimura
  • Chiharu Tohyama
Molecular Toxicology


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.


Attachment behavior Developmental neurotoxicity Dioxin Infant behavior Ultrasonic vocalization 



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.).

Compliance with ethical standards

Conflict of interest

The authors declare no competing financial interests.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of MedicineThe University of TokyoTokyoJapan
  2. 2.Center for Health and Environmental Risk ResearchNational Institute for Environmental StudiesTsukubaJapan
  3. 3.Research Fellow of Japan Society for the Promotion of ScienceTokyoJapan
  4. 4.Faculty of MedicineUniversity of TsukubaTsukubaJapan

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