title: Prenatal low dosage dioxin (TCDD) exposure impairs cochlear function resulting in auditory neuropathy.
abstract: 2,3,7,8-tetrachorodibenzo-p-dioxin (TCDD), a ubiquitous and persistent environmental contaminant, is a potent teratogen. Whereas developmental TCDD toxicity is mediated by the aryl hydrocarbon receptor (AhR), the normal function of the AhR is poorly understood. We tested whether dioxin exposure during a critical period of hair cell development disrupts cochlear function in three mouse strains, (C57BL6, BalbC, and CBA) that contain high affinity AhR-b alleles. C57BL/6, BalbC, and CBA dams were exposed to 500 ng/kg TCDD or olive oil (vehicle) on embryonic day 12 by gavage. Cochlear function was analyzed at 1.5 months of age by measuring 1) auditory brainstem response (ABRs) to tone pips from 5.6 to 30 kHz, and 2) distortion-product otoacoustic emissions (DPOAEs) evoked by primaries with f2 at the same frequency values. Cochlear threshold sensitivity following TCDD exposure was significantly elevated in both female and male mice in the C57BL/6 strain, carrying the Ahb-1 allele, but not significantly elevated in the BalbC or CBA strains, carrying the Ahb-2 allele. These ABR threshold deficits in mice carrying the Ahb-1 allele parallels the cleft palate incidence to higher TCDD exposures, suggesting that ABR testing could serve as a sensitive indicator of TCDD toxicity in at-risk children. Moreover, DPOAEs were not affected following TCDD exposure in any of the mouse strains, suggesting that following TCDD exposure mice with the Ahb-1 allele exhibit a mild auditory neuropathy. The causes of many auditory neuropathies are unknown, yet a developmental exposure to dioxin may be a risk factor for this condition.
authors.affiliation: Department of Biomedical Engineering, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Safe
authors.affiliation: Department of Biomedical Engineering, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA; Department of Neurobiology & Anatomy, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA. Electronic address: anne_luebke@urmc.rochester.edu.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Luebke
mesh_terms: D000483:Alleles; D000818:Animals; D003051:Cochlea / Q000187:drug effects* / Q000502:physiology; D004147:Dioxins / Q000737:chemistry; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005260:Female; D006313:Hearing Loss, Central / Q000139:chemically induced* / Q000503:physiopathology*; D006838:Hydrocarbons / Q000737:chemistry; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D017084:Otoacoustic Emissions, Spontaneous; D000072317:Polychlorinated Dibenzodioxins / Q000009:adverse effects*; D011247:Pregnancy; D011270:Pregnancy, Animal; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics; D012307:Risk Factors; D013723:Teratogens
chemical_list: D004147:Dioxins; D006838:Hydrocarbons; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D013723:Teratogens
keywords: ABR; Ah b1 allele; Auditory neuropathy; Cochlea; DPOAE; Dioxin; High affinity aryl hydrocarbon receptor; Mouse; TCDD