Folic acid rescues all‐trans retinoic acid‐induced anorectal malformations in rats

Abstract

Background: To investigate whether folic acid (FA) can rescue anorectal malformations (ARMs) induced by all-trans retinoic acid (ATRA) in rats. Methods: Pregnant Sprague-Dawley rats were randomly divided into three groups. In the model group, rats were administered ATRA (110 mg/kg) by gavage on the 10th day of gestation (E10.5). Rats in the rescue group were administered FA (40 mg/kg) by gavage 0.5 and 12 hr after treatment with ATRA. All fetuses were harvested on E20.5 using cesarean section and examined for ARMs. We recorded the weight, body length, tail length, and associated malformations of all the embryos. Hematoxylin and eosin staining was used to analyze the histopathology of the fetuses. Results: Control rats did not show any abnormalities. ARMs, tail deformities (less than half of normal length), and neural tube defects were found in 97.98% (97/99), 92.93% (92/99), and 32.32% (32/99) of the rats in the model group, respectively. The incidence of ARMs and tail deformities were 48.57% (51/105) and 35.24% (37/105), respectively, in the rescue rats; no neural tube defects were observed in these rats. The weight, body length, and tail length of the fetal rats in the rescue group were more than those in the model group, but less than those in the control group. Conclusion: Taken together, FA rescued ARMs induced by ATRA in rats. Thus, FA may reduce the incidence of associated malformations and improve the growth and development of fetal rats.

Investigation of the risk factors of anorectal malformations

“…Results of the multivariate logistic regression analysis revealed that folic acid and multivitamin supplementation may be protective factors for ARMs. In animal models, folic acid was shown to prevent ARMs induced by different teratogens in rats (Faria, Simões Mde, & Martins, 2015; Wu, Gu, Bi, Guo, & Wang, 2020). However, a previous Dutch study did not find any association of folic acid and multivitamin supplementation with ARMs (van Rooij et al, 2010).…”