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EFFECTS OF GESTATIONAL EXPOSURE TO ETHANE DIMETHANESULFONATE IN CD-1 MICE: MICROTIA AND PRELIMINARY HEARING TESTS
Citation:
Tarka, D. K., D W. Herr, G R. Klinefelter, AND J M. Rogers. EFFECTS OF GESTATIONAL EXPOSURE TO ETHANE DIMETHANESULFONATE IN CD-1 MICE: MICROTIA AND PRELIMINARY HEARING TESTS. BIRTH DEFECTS RESEARCH PART B: DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY 68(4):383-390, (2003).
Description:
Microtia is a reduction in pinna size, usually seen in humans in conjunction with other medical conditions. Here we report microtia in CD-1 mice following gestational exposure to ethane dimethanesulfonate (EDS), an alkylating agent and adult rat Leydig cell toxicant. Methods: Time-pregnant CD-1 mice were administered 0, 80, or 160 mg EDS/kg on gestation days (GD) 11-17, or 0 or 160 mg EDS/kg on GD 11-13, GD 13-15 or GD 15-17. Pinnae were measured on postnatal days (PND) 4, 8, 18, and 28; and were observed for detachment from birth through PND 8. Branchial-arch derived skeletal structures and histology of the pinna was examined on PND 4 and 24. Brainstem auditory evoked response (BAER) tests were performed at approximately PND160 to determine possible effects on hearing. Results: All offspring of EDS-treated dams exhibited bilateral, dose-related decreases in pinna size. Gestational exposure during GD 11-13 produced smaller ears than during GD 13-15 or 15-17, but not as small as the GD 11-17 regimen. Ossification of other pharyngeal arch derivatives was delayed, while histology was unremarkable. BAER analysis revealed a decrease in the proportion of adult offspring producing a quantifiable response to varied auditory stimuli among EDS-treated litters. Conclusions: Gestational exposure to EDS affects pinna development in the mouse, with a broad period of sensitivity during the second half of gestation. Microtia induced by EDS may be associated with hearing deficits, suggesting functional importance of pinna size and/or additional effects of EDS on ear development not detected by morphological examination.