Abnormal serum vitamin A levels and retinoic acid receptor α expression patterns in children with anorectal malformation

  • Zhili Wang
  • Quan Wang
  • Chengchao Gu
  • Jingjie Zhang
  • Yi WangEmail author
Original Article



Anorectal malformation (ARM) is known to be associated with maldevelopment of the enteric nervous system (ENS), and vitamin A (VA) and its metabolite retinoic acid (RA) play important roles in ENS development. Thus, our aim was to investigate serum VA levels in ARM newborns and RA receptor (RAR) expression in the rectum of ARM patients and animal models.


Serum VA concentrations were detected in newly diagnosed ARM neonates (n = 32) and neonates with non-alimentary tract malformations (n = 30). Intestinal specimens were divided into three groups: rectum from ARM patients (n = 30), colon from a stoma (n = 30) and rectum from controls (n = 4). RAR mRNA expression was evaluated by RT-qPCR. Rectum specimens from ARM patients were divided into two groups by postoperative pathology: the normal and lesion ganglion cell groups. Immunohistochemistry and Western blot were employed to detect RARα protein expression in rectum specimens. In addition, the ARM mouse model was induced by all-trans retinoid acid (ATRA), and the expression levels of RARα and the neuronal marker NeuN in the rectum of mice on embryonic day 16.5–18.5 (E16.5–18.5) were investigated.


The serum concentration of VA in ARM neonates was lower than that in control neonates (P < 0.0001), and RARα mRNA expression was lower in the rectum specimens from ARM patients than in the colon specimens from a stoma and the rectum specimens from controls (P < 0.05); there was no significant difference between the colon from a stoma and the rectum from controls. RARα protein was expressed in the nucleus of ganglion cells and nerve fibers, and RARα protein expression in the lesion ganglion cell group was significantly lower than that in the normal ganglion cell group (P < 0.01). Compared with the control mice, ARM mice at E16.5–18.5 showed decreased fluorescence intensity of RARα and NeuN in the rectum. RARα and NeuN mRNA expression in the rectum on E16.5–18.5 was lower in ARM mice than in control mice (P < 0.05).


Serum VA concentration and the RARα expression pattern are abnormal in the rectum in ARM and may contribute to the ENS maldevelopment in ARM.


Anorectal malformation Enteric nervous system Vitamin A Retinoic acid receptor 



Supported by Natural Science Foundation Project of CQ CSTC (cstc2018jcyjA0340).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Consent to publish

All authors have read and approved the manuscript.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Zhili Wang
    • 1
  • Quan Wang
    • 2
  • Chengchao Gu
    • 1
  • Jingjie Zhang
    • 1
  • Yi Wang
    • 1
    Email author
  1. 1.Department of Neonatal Gastrointestinal Surgery, Children’s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of PediatricsChongqingChina
  2. 2.Department of Cardiothoracic SurgeryChildren’s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of PediatricsChongqingChina

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