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Hearing Loss from pre- and postnatal retinoic acid exposure: Critical periods of exposure
NEUROBEHAVIORAL
TERATOLOGY
SOCIETY ABSTRACTS
methanol, 48 adult female Macaca fascicularis were exposed to either 0, 200,600, or 1800 ppm methanol, 7 days per week, prior to and throughout pregnancy. Females were bred with nonexposed males. Beginning at birth and continuing through the first year of life, infants were evaluated on a series of tests including early reflex development, visual recognition memory, object permanence, visual acuity, social behavior, learning, and physical growth. The first cohort of infants completed this test battery about a year ago and the second cohort is currently under study. Results from the first cohort suggested subtle effects of MeOH on gestation length, visually guided reaching, and visual recognition memory for complex stimuli. Most assessments however, failed to reveal a MeOH related effects. All infants from the second cohort are now born and currently being evaluated. The final results from both cohorts will be presented. (Supported by grant #90-9 from the Health Effects Institute and grant # ES06773 from NIEHS)
NBTS 24 CHURCH, M.W. and G.W. OVERBECK*, Dept. Obstet. Gynecol., Wayne State Univ. Sch. Med., Detroit, Michigan. Hearing loss from pre- and postnatal cocaine exuosure: Critical ueriods of exuosure. Evidence suggests that the inner ear may be susceptible to prenatal cocaine exposure (Church & Overbeck, 1990, 199 1). We sought to confirm and extend these observations by evaluating the effects of pre- and postnatal cocaine exposure on auditory function. Long-Evans rats were prenatally exposed to cocaine HCl on GD 7-13 or GD 14-20 by giving (s.c.) 30 mg/kg twice daily to pregnant dams or postnatally on PD lo- 16 by giving 60 mg/kg once daily directly to the pups. Untreated and pairfed/saline-injected control groups were also used. Hearing was evaluated in adulthood auditory brainstem responses (ABR) (n = 9-14/group, one per litter). Instances of hearing impairment, in the form of sensorineural hearing loss, were produced by only early prenatal (GD 7- 13) cocaine exposure. This contrasts with ocular defects which can be produced by late gestational (GD 14-20) exposure but not by earlier exposure (Church et al., 1996; Webster et al., 1991). This was somewhat surprising because the teratogenic effects of cocaine
335
occur mostly in late gestation when the fetal vasculature is more developed, thus allowing anoxia and hemorrhaging to occur from cocaine-induced vasoconstriction. (Supported by NIDA grant DA 05536).
NBTS 25 CHURCH, M.W. and G.W. OVERBECK*, Dept. Obstet. Gynecol., Wayne State Univ. Sch. Med., Detroit, Michigan. &np Loss from pre- and postnatal retinoic acid exposure: Critical neriods of s;xDosure. There is increased use of retinoids from skin creams (Accutane, Retin-A), dietary supplements (vitamin A), and as treatments for retinitis pigmentosa (RP) (retinyl palmitate) and cancer (retinoic acid). This is disturbing because even moderate increases in dietary retinoids can augment the risk for birth defects (Rothman et al., 1995). Ear malformations, for example, can be caused by early gestational retinoid exposure. Nothing, however, is known about possible auditory defects caused by late gestational or postnatal exposure. The effects of postnatal exposure would be particularly important for children receiving retinoid therapy, such as RP patients. Consequently, Long-Evans rats were prenatally exposed to all-trans-retinoic acid (RA) by giving (p.0.) 10 m&g to the dams on GD 7-6 or GD !4- 16 or postnatally by giving RA directly to the pups on PD 1O-12. Control groups were also used. Hearing was evaluated in adulthood by auditory brainstem responses (ABR) (n = 9-12/group, one per litter). Instances of sensorineural hearing loss were caused by R4 during all three exposure periods. Thus, retinoids have the potential to cause inner ear damage during several developmental stages, raising concerns about hearing impairment in children from postnatal as well as prenatal exposure to retinoid excess. (Supported by NIDA grant DA 05536).
NBTS 26 FUKUMURA*, M., N. SETHI* and C.V. VORHEES. Division of Developmental Biology, Children’s Hospital Res. Found. and Univ. of Cincinnati, Cincinnati, Ohio. . 3.3’-Iminodiuropionittile (IDPNI-induced neutoxicrtv; Comuarison of two methods of detecti--induced _ ‘v’ttv in rata aartle impairment and accompa nvine_ hyueracti
TERATOLOGY
SOCIETY ABSTRACTS
methanol, 48 adult female Macaca fascicularis were exposed to either 0, 200,600, or 1800 ppm methanol, 7 days per week, prior to and throughout pregnancy. Females were bred with nonexposed males. Beginning at birth and continuing through the first year of life, infants were evaluated on a series of tests including early reflex development, visual recognition memory, object permanence, visual acuity, social behavior, learning, and physical growth. The first cohort of infants completed this test battery about a year ago and the second cohort is currently under study. Results from the first cohort suggested subtle effects of MeOH on gestation length, visually guided reaching, and visual recognition memory for complex stimuli. Most assessments however, failed to reveal a MeOH related effects. All infants from the second cohort are now born and currently being evaluated. The final results from both cohorts will be presented. (Supported by grant #90-9 from the Health Effects Institute and grant # ES06773 from NIEHS)
NBTS 24 CHURCH, M.W. and G.W. OVERBECK*, Dept. Obstet. Gynecol., Wayne State Univ. Sch. Med., Detroit, Michigan. Hearing loss from pre- and postnatal cocaine exuosure: Critical ueriods of exuosure. Evidence suggests that the inner ear may be susceptible to prenatal cocaine exposure (Church & Overbeck, 1990, 199 1). We sought to confirm and extend these observations by evaluating the effects of pre- and postnatal cocaine exposure on auditory function. Long-Evans rats were prenatally exposed to cocaine HCl on GD 7-13 or GD 14-20 by giving (s.c.) 30 mg/kg twice daily to pregnant dams or postnatally on PD lo- 16 by giving 60 mg/kg once daily directly to the pups. Untreated and pairfed/saline-injected control groups were also used. Hearing was evaluated in adulthood auditory brainstem responses (ABR) (n = 9-14/group, one per litter). Instances of hearing impairment, in the form of sensorineural hearing loss, were produced by only early prenatal (GD 7- 13) cocaine exposure. This contrasts with ocular defects which can be produced by late gestational (GD 14-20) exposure but not by earlier exposure (Church et al., 1996; Webster et al., 1991). This was somewhat surprising because the teratogenic effects of cocaine
335
occur mostly in late gestation when the fetal vasculature is more developed, thus allowing anoxia and hemorrhaging to occur from cocaine-induced vasoconstriction. (Supported by NIDA grant DA 05536).
NBTS 25 CHURCH, M.W. and G.W. OVERBECK*, Dept. Obstet. Gynecol., Wayne State Univ. Sch. Med., Detroit, Michigan. &np Loss from pre- and postnatal retinoic acid exposure: Critical neriods of s;xDosure. There is increased use of retinoids from skin creams (Accutane, Retin-A), dietary supplements (vitamin A), and as treatments for retinitis pigmentosa (RP) (retinyl palmitate) and cancer (retinoic acid). This is disturbing because even moderate increases in dietary retinoids can augment the risk for birth defects (Rothman et al., 1995). Ear malformations, for example, can be caused by early gestational retinoid exposure. Nothing, however, is known about possible auditory defects caused by late gestational or postnatal exposure. The effects of postnatal exposure would be particularly important for children receiving retinoid therapy, such as RP patients. Consequently, Long-Evans rats were prenatally exposed to all-trans-retinoic acid (RA) by giving (p.0.) 10 m&g to the dams on GD 7-6 or GD !4- 16 or postnatally by giving RA directly to the pups on PD 1O-12. Control groups were also used. Hearing was evaluated in adulthood by auditory brainstem responses (ABR) (n = 9-12/group, one per litter). Instances of sensorineural hearing loss were caused by R4 during all three exposure periods. Thus, retinoids have the potential to cause inner ear damage during several developmental stages, raising concerns about hearing impairment in children from postnatal as well as prenatal exposure to retinoid excess. (Supported by NIDA grant DA 05536).
NBTS 26 FUKUMURA*, M., N. SETHI* and C.V. VORHEES. Division of Developmental Biology, Children’s Hospital Res. Found. and Univ. of Cincinnati, Cincinnati, Ohio. . 3.3’-Iminodiuropionittile (IDPNI-induced neutoxicrtv; Comuarison of two methods of detecti--induced _ ‘v’ttv in rata aartle impairment and accompa nvine_ hyueracti