Structure and function of the adult inner ear in the mouse following prenatal irradiation

The function and morphology of the vestibular and cochlear parts of the inner ear have been examined after prenatal irradiation on the 12th, 13th and 16th gestational days in the CBA/CBA mouse. Irradiation was performed with a 0.5, 1 or 2 Gy single dose, whole body irradiation of the pregnant female. The irradiated fetuses were born after full term pregnancies and reached maturity (were 1--2 months old) before inner ears were analyzed with regard to vestibular tests, auditory thresholds and morphology. Morphology was studied by light microscopy (LM), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Auditory function was analyzed by frequency specific auditory brainstem response (ABR). Irradiation doses exceeding 2 Gy caused death to the pregnant female, abortion or malformed litters which were eaten by their mothers. Doses of 0.5, 1 and 2 Gy caused malformed cristae ampullares and maculae utriculi, in particular after exposure on the 12th or 13th gestational days. After those doses no abnormality of clinical behaviour of the animals was found. Ultrastructurally, type I hair cells (HC) of the vestibular part seemed more vulnerable to irradiation than the type II HC while the outer (OHC) and inner (IHC) hair cells appeared equally vulnerable. The ultrastructural changes of hair cells were predominantly localized to the hair cell surface showing a defect cuticle which was sometimes malformed and bulging. Sensory hair fusion occurred with a resulting poor maturation of sensory hair rootlets. The efferent nerve endings were estimated to be reduced in number but, if present, they had a normal ultrastructure. Otoconia showed severe morphological damage following irradiation particularly if exposed on the 16th gestational day. Malformed and fused otoconia were frequent having a disarrayed matrix. The irradiation induced morphological alterations in vivo could be reproduced in the in vitro systems. In addition, a retarded growth of the in vitro developing inner ear anlage was estimated to be the same for the vestibular and cochlear parts. The cochlear part of the inner ear showed a dose and age dependent hearing loss following irradiation. A shift of the ABR threshold was recorded in all exposed groups that were irradiated with 2 Gy. A correlation was found between the individual ABR-audiograms and the degree of morphological HC damage in the cochlea along the basilar membrane. The 12th gestational day inner ear anlage was most vulnerable to irradiation. The 13th gestational day inner ear was almost equally vulnerable and showed a dose-response relationship.(ABSTRACT TRUNCATED AT 400 WORDS)