Eldeib M M, Reddy C S
Department of Veterinary Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia 65211.
Teratology. 1990 Feb;41(2):137-46. doi: 10.1002/tera.1420410203.
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.
变色曲酸D（SAD）是一种致畸性霉菌毒素，可导致经处理的怀孕小鼠后代出现腭裂。为了研究母体皮质酮在SAD致畸性中的作用，在妊娠第11天，给怀孕的CD-1小鼠腹腔注射30mg/kg的SAD，溶剂为5%（w/v）的碳酸氢钠或含20%（v/v）二甲基亚砜（DMSO）的碳酸氢钠。给药后24、48、72和96小时进行放射免疫分析（RIA）以测定血浆皮质酮。未发现EDTA、SAD、DMSO或戊巴比妥对RIA有干扰。在以碳酸氢钠为溶剂给小鼠注射SAD后24和48小时，血浆皮质酮浓度显著（P<0.01）升高，在腭架抬高和融合开始前达到峰值。同时用已知可拮抗SAD致畸作用的DMSO进行处理，在24小时时间点完全消除了SAD诱导的皮质酮升高，并在48小时时间点显著（P<0.01）降低了皮质酮升高。为了评估皮质酮在SAD致畸性中作用的特异性，对同样接受单剂量或多剂量（15至45mg/kg）SAD处理的成年雄性小鼠的血浆样本进行皮质酮检测。与给怀孕雌性小鼠使用的剂量相当的SAD剂量未能显著改变雄性小鼠的血浆皮质酮浓度。接受多剂量SAD（总量为给雌性小鼠使用剂量的三倍）的雄性小鼠中，皮质酮升高仅相当于雌性小鼠的75%。与雌性小鼠一样，DMSO完全消除了雄性小鼠中SAD引起的血浆皮质酮升高。这些结果首次证明了SAD对哺乳动物内分泌系统的影响，并为母体血浆皮质酮浓度升高在SAD致畸性中的特定作用提供了证据。
