Toxicol Res.  2013 Sep;29(3):173-179.

Gastrointestinal Tract Abnormalities Induced by Prenatal Valproic Acid Exposure in Rat Offspring

• Kim JW
• Choi CS
• Kim KC
• Park JH
• Seung H
• Joo SH
• Yang SM
• Shin CY
• Park SH

Abstract

In-utero exposure to valproic acid (VPA) has been known as a potent inducer of autism spectrum disorder (ASD), not only in humans, but also in animals. In addition to the defects in communication and social interaction as well as repetitive behaviors, ASD patients usually suffer from gastrointestinal (GI) problems. However, the exact mechanism underlying these disorders is not known. In this study, we examined the gross GI tract structure and GI motility in a VPA animal model of ASD. On embryonic day 12 (E12), 4 pregnant Sprague-Dawley (SD) rats were subcutaneously injected with VPA (400 mg/kg) in the treatment group, and with phosphate buffered saline (PBS) in the control group; the resulting male offspring were analyzed at 4 weeks of age. VPA exposure decreased the thickness of tunica mucosa and tunica muscularis in the stomach and ileum. Other regions such as duodenum, jejunum, and colon did not show a significant difference. In high-resolution microscopic observation, atrophy of the parietal and chief cells in the stomach and absorptive cells in the ileum was observed. In addition, decreased staining of the epithelial cells was observed in the hematoxylin and eosin (H&E)-stained ileum section. Furthermore, decreased motility in GI tract was also observed in rat offspring prenatally exposed to VPA. However, the mechanism underlying GI tract defects in VPA animal model as well as the association between abnormal GI structure and function with ASD is yet to be clearly understood. Nevertheless, the results from the present study suggest that this VPA ASD model undergoes abnormal changes in the GI structure and function, which in turn could provide beneficial clues pertaining to the pathophysiological relevance of GI complications and ASD phenotypes.

Keyword

Valproic acid; ASD; GI motility; GI thickness; Epithelial cells

MeSH Terms

Animals
Atrophy
Child
Autism Spectrum Disorder
Colon
Duodenum
Eosine Yellowish-(YS)
Epithelial Cells
Gastrointestinal Tract*
Hematoxylin
Humans
Ileum
Interpersonal Relations
Jejunum
Male
Models, Animal
Mucous Membrane
Phenotype
Rats*
Stomach
Valproic Acid*
Eosine Yellowish-(YS)
Hematoxylin
Valproic Acid