Bolon B, St Omer V E
Department of Veterinary Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia 65211.
Pharmacol Biochem Behav. 1989 Oct;34(2):229-36. doi: 10.1016/0091-3057(89)90304-3.
Pregnant mice (dams) were gavaged once on gestational day 13 with 4 ml/kg of dimethylsulfoxide vehicle containing 0 (groups 15, 25 and negative control) or 25 (positive behavioral teratogenic control group) mg/kg of secalonic acid D (SAD). While nursing their offspring, dams were gavaged on postgestational days 1 to 10 with vehicle containing 0 (negative and positive control groups), 15 (group 15) or 25 (group 25) mg/kg/day of SAD. Gestational lengths, maternal pregnancy weights, litter sizes, neonatal sex ratios, neonatal physical appearance and female birth weights were unaffected by prenatal treatment, but male pups born to positive control dams weighed less (p less than 0.05) than negative control group. Compared to negative control, the positive control dams gained significantly more weight while nursing their offspring. Prenatal (positive control) and postnatal (15, 25) SAD exposure delayed ontogeny of surface righting, olfactory discrimination and hindlimb grip behaviors in males and females, and testes descent in males. Negative geotaxis in male and female offspring of group 25 and male offspring of positive control group, as well as times of incisor eruptions of both sexes in groups 15 and 25 were delayed. A significant dose-response effect in olfactory discrimination existed between the groups exposed to postnatal SAD. SAD was behaviorally teratogenic following both prenatal and early postnatal exposure.
怀孕小鼠(母鼠)在妊娠第13天经口灌胃一次,给予每千克体重4毫升含0毫克/千克(第15组、第25组和阴性对照组)或25毫克/千克(阳性行为致畸对照组)的二甲基亚砜载体溶液的海柯皂苷元D(SAD)。在哺育后代期间,母鼠在产后第1至10天经口灌胃给予含0毫克/千克/天(阴性和阳性对照组)、15毫克/千克/天(第15组)或25毫克/千克/天(第25组)SAD的载体溶液。妊娠长度、母鼠孕期体重、窝仔数、新生仔鼠性别比、新生仔鼠外观及雌性仔鼠出生体重均不受产前处理的影响,但阳性对照组母鼠所生雄性幼仔体重低于阴性对照组(p<0.05)。与阴性对照组相比,阳性对照组母鼠在哺育后代期间体重增加显著更多。产前(阳性对照组)和产后(第15组、第25组)暴露于SAD会延迟雄性和雌性幼仔的表面翻正、嗅觉辨别和后肢抓握行为的个体发育,以及雄性幼仔的睾丸下降。第25组的雄性和雌性后代以及阳性对照组的雄性后代的负趋地性,以及第15组和第25组两性的门齿萌出时间均延迟。产后暴露于SAD的各组之间在嗅觉辨别方面存在显著的剂量反应效应。产前和产后早期暴露于SAD均具有行为致畸性。