Role of maternal plasma corticosterone elevation in the teratogenicity of secalonic acid D in mice.
Secalonic acid D (SAD) is a teratogenic mycotoxin that causes cleft palate in the offspring of treated pregnant mice. To investigate the role of maternal corticosterone in the teratogenicity of SAD, pregnant CD-1 mice were treated with 30 mg/kg of SAD i.p. on day 11 of pregnancy in either 5% (w/v) NaHCO3 or 20% (v/v) dimethyl sulfoxide (DMSO) in NaHCO3. Radioimmunoassay (RIA) was performed to determine plasma corticosterone at 24, 48, 72, and 96 hr after dosing. No interference by EDTA, SAD, DMSO, or pentobarbital was noticed on the RIA. Significant (P less than .01) elevations in plasma corticosterone concentrations were seen 24 and 48 hr following dosing of SAD in NaHCO3 with concentrations reaching a peak just prior to the onset of shelf elevation and fusion. Simultaneous treatment with DMSO, an agent known to antagonize the teratogenic effect of SAD, completely abolished the SAD-induced corticosterone elevation at the 24 hr time point and significantly (P less than .01) reduced it at the 48 hr time point. To evaluate the specificity of the role of corticosterone in the teratogenicity of SAD, plasma samples from mature males similarly treated with either single or multiple doses of SAD ranging from 15 to 45 mg/kg were assayed for corticosterone. A dose of SAD comparable to that used in the pregnant females failed to significantly change plasma corticosterone concentrations in the males. An elevation corresponding only to 75% of that in the females was seen in males receiving multiple doses of SAD totaling three times the dose used in the females. As with females, DMSO completely abolished plasma corticosterone elevation by SAD in the males. These results demonstrate, for the first time, the effect of SAD on a mammalian endocrine system and provide evidence for a specific involvement of elevated maternal plasma corticosterone concentrations in SAD teratogenicity.
Eldeib
M M
MM
Department of Veterinary Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia 65211.
Reddy
C S
CS
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000818:Animals; D002972:Cleft Palate / Q000139:chemically induced*; D003345:Corticosterone / Q000097:blood*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008431:Maternal-Fetal Exchange; D051379:Mice; D011247:Pregnancy; D011863:Radioimmunoassay; D014966:Xanthenes / Q000633:toxicity*; D044004:Xanthones
D014966:Xanthenes; D044004:Xanthones; C009218:secalonic acid; D003345:Corticosterone; D004121:Dimethyl Sulfoxide