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Teratogenic effects of the anticonvulsant drug valproic acid (VPA) on the development of rat embryos during early stage of organogenesis were studied using whole embryo culture technique. Embryos with 0-3 somites were exposed in culture to 10, 50 and 100 μg/ml VPA. Growth and development were retarded in embryos exposed to 50 and 100 μg/ml. Drug induced anomalies included open neural tube, irregular somites, and asymmetrically enlarged forebrain. The "no-observed-adverse-effect-level" (NOAEL) was 10 μg/ml VPA.
Embryonic cells, when cultured at high density, are referred to as „micromass” cultures and can be used as a tool to predict the teratogenic potential of xenobiotics in screen test. The rate of proliferation and differentiation can easily be measured quantitatively by simple staining methods with subsequent spectrophotometry. However, reproducibility of the results can be influenced by variability of the technique. To adapt this method in our laboratory systematic series of experiments with limb bud cell cultures were undertaken. Inter-relationships between different variables were checked.
Administration of the Ascaris tegumental homogenate (0.6-1.2 g of Ascaris proteins/kg/day) at a early stage of organogenesis (5-9 days of pregnancy) had a harmful effect upon the developing mouse fetuses. It has been found that injection of the homogenate did not delay or prevent implantation, but causes a high rate of intrauterine deaths. The Ascaris homogenate significantly decreased the number of live fetuses per litter, increased the frequency of litter resorption, produced a delay in bone formation and induced pathological changes of fetal organs and tissues. The congenital malformations were noted in fetuses after injection of higher doses of Ascaris homogenate (exencephaly, craniomeningocele and intemal hydrocephalus). No malformations were noted in control groups and after injection of minimum dose of the homogenate. The symptoms that occurred after administration of the tegumental homogenate to pregnant mice included: decreased body weight gain (p<0.001) as compared to controls, vaginal hemorrhage, intrauterine resorption of litter and mortality. These signs suggest that the Ascaris homogenate causes matemal toxicity.
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