Congenital Malformations in a VPA-Induced Rat Model of Autism Spectrum Disorder

Autism is a disorder with a spectrum of behavioral, developmental and neurological symptoms and has genetic and environmental etiology. Prenatal exposure to valproic acid (VPA) induces autism like symptoms in rodents and it is a favored model because of its similar aspects in humans. 8 pregnant Wistar albino rats were used in this study. 5 of them received 400 mg/kg/ml VPA and 3 of them received same volume of vehicle on E12,5. 79 offsprings (nVPA: 48, nctrl: 31) were grossly examined on P22. Among 48 of the VPA exposed pups, 30 of them showed physical malformations whereas there were no malformations observed in the control group. Displayed malformations are as follows; tail bends in 22 out of 48 (45,83%), extra digit-like paw malformations in 8 out of 48 (16,66%) and position deformity with motor strength loss in foot in 1 out of 48 (2,08%). Distribution of the malformations among sexes was insignificant. Bends in tails were characterized by location and severity. Proximal tail bends were more common than middle and distal locations. Our results support the teratogenic effects of in utero VPA exposure which were seen as physical malformations. Further studies are required to unreveal possible correlations of malformations with behavioral symptoms. Our findings enhance the facial validity of VPA induced models of autism and broaden model’s symptomatic spectrum