Objective To supplement the DevTox database with various embryonic skeletal malformation images of SD rats by constructing a rat model using retinoic acid (RA) and assessing the dose-response relationship between RA and malformation
Methods Pregnant SD rats were administered via gavage on gestational day (GD) 10 with RA at doses of 50, 100, and 150 mg/kg or with corn oil. After the animals were executed on GD 20, the details of embryo implantation and development in each group were observed and recorded. After embryo bones were stained by alizarin red for identifying skeletal malformation in each body part, the incidence of bone deformity was calculated and the identified malformation site images were taken under anatomical microscope.
Results Multiple abnormalities in embryo bones were clearly observed in all three RA-treated groups with teratogenetic rates up to 100%. The main abnormalities included dagnathia, fusion of maxilla and zygomatic arch, sternothyma, deficiency or fusion of thoracic vertebra section 10-13, deficiency or fusion of lumbar vertebra, deficiency of pelvic girdle and caudal vertebra. The phenotype and occurrence rate of abnormalities in the three RA-treated groups were highly consistent and repeatable, the rates of embryo abnormalities among the three dose groups were all 100%, but the degrees of abnormalities increased with higher doses. The collected images of normal and abnormal bones were clear and free from bubbles and reflections with high resolution.
Conclusion Severe skeletal malformations are identified in SD rat embryos after maternal exposure to RA on GD10 at 50 mg/kg and above, showing a high malformation rate and various abnormality types. The images of skeletal malformation could supplement the DevTox database.
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