Role of maternal plasma corticosterone elevation in the teratogenicity of secalonic acid D in mice.
Role of maternal plasma corticosterone elevation in the teratogenicity of secalonic acid D in mice.
复制标题
母体血浆皮质酮升高在小鼠癸二酸 D 致畸性中的作用。
DOI：
10.1002/tera.1420410203
复制
发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Reddy,CS
中科院分区：
文献类型：
--
作者：
Eldeib,MM;Reddy,CS
Secalonic acid D（SAD）是一种致畸性真菌毒素，可导致经处理的妊娠小鼠的后代出现腭裂。为了研究母体皮质酮在SAD致畸性中的作用，妊娠CD-1小鼠在妊娠第11天接受30 mg/kg SAD i.p.（溶于5%（w/v）NaHCO3或20%（v/v）二甲亚砜（DMSO）的NaHCO3溶液）处理。在给药后24、48、72和96小时进行放射免疫测定（RIA）以测定血浆皮质酮。EDTA、SAD、DMSO或戊巴比妥对RIA无干扰。在NaHCO3中SAD给药后24和48小时，血浆皮质酮浓度显著升高（P <0.01），浓度在货架升高和融合开始前达到峰值。同时用DMSO（一种已知拮抗SAD致畸作用的药物）处理，在24小时时间点完全消除SAD诱导的皮质酮升高，并在48小时时间点显著降低（P <0.01）。为了评价皮质酮在SAD致畸性中作用的特异性，对来自成年雄性的血浆样品进行皮质酮分析，所述血浆样品类似地用范围为15至45 mg/kg的SAD单次或多次给药。SAD的剂量相当于在怀孕的女性中使用的没有显着改变血浆皮质酮浓度的男性。在接受SAD多次给药的雄性动物中观察到的升高仅相当于雌性动物的75%，SAD多次给药的剂量总计为雌性动物所用剂量的3倍。与女性一样，DMSO完全消除了男性SAD引起的血浆皮质酮升高。这些结果表明，第一次，SAD对哺乳动物内分泌系统的影响，并提供了证据，特别是参与母亲血浆皮质酮浓度升高SAD致畸性。
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) NaHCO3or 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< .01) elevations in plasma corticosterone concentrations were seen 24 and 48 hr following dosing of SAD in NaHCO3with 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< .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.