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Eur J Pediatr Surg 2019; 29(04): 368-370
DOI: 10.1055/s-0039-1694743
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Anorectal Malformation: State of the Art in Translating Experimental Research to the Bedside

José Luiz Martins 
1   Department of Surgery, Universidade Federal de Sao Paulo Escola Paulista de Medicina, São Paulo, Brazil
,
Maurício Macedo
2   Department of Pediatric Surgery, Hospital Infantil Darcy Vargas, São Paulo, Brazil
,
Edna Frasson de Souza Montero
3   Department of Gastroenterological Surgery, Universidade Federal de Sao Paulo Escola Paulista de Medicina, Sao Paulo, Brazil
› Author Affiliations
Further Information

Publication History

28 June 2019

08 July 2019

Publication Date:
19 August 2019 (online)

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Abstract

The embryology of anorectal malformation (ARM) is a controversial issue. The study in humans is difficult due to the scarcity of fetuses with this anomaly. Therefore, ARM animal models, naturally obtained or induced by drugs, have been employed to understand physiopathology and possible treatments. Pigs, rabbits, rats, and mice have been employed as animal models. Additionally, many drugs have been used with this purpose: Etretinate, Ethylenethiourea, and Adriamycin. The animal more frequently used is the rat because of good reproducibility, low cost, and easy handling. Pig is a good model, but it is expensive, and difficult to handling and lodging. Concerning the drugs, Adriamycin promotes a more severe ARM compared with Ethylenethiourea. The models of ARM are of value in the understanding of the embryologic development. Nowadays, researches are aimed at identifying the molecular mechanism of this process, providing the basis for the application of tissue engineering in future experiments with ARM.

Keywords

anorectal malformations - experimental models - ethylenethiourea - adriamycin
 

  • References

  • 1 Stephens FD, Smith ED. Anorectal Malformations in Children. Chicago IL: Year Book Medical Publishers; 1971
    Google Scholar
  • 2 Rathke H. AbhandlungenzurBildungs-und Entwicklungsgeschichte der Tiere. Leipzig: F.C.W. Vogel; 1832
    Google Scholar
  • 3 Tourneux F. Sur les premiers dévelopments du cloaque du tubercle genitale et de l'anus chez l'embryon de mouton. J Anat (Paris) 1888; 24: 503-517
    PubMedGoogle Scholar
  • 4 Retterer E. Sur l'órigine et évolution de la région ano-génitale des mammifères. J Anat (Paris) 1890; 26: 126-216
    PubMedGoogle Scholar
  • 5 Stephens FD, Smith ED. Anorectal Malformations in Children: Update. New York, NY: Alan R. Liss, Inc.; 1988
    Google Scholar
  • 6 van der Putte SCJ, Neeteson FA. The normal development of the anorectum in the pig. Acta Morphol Neerl Scand 1983; 21 (02) 107-132
    PubMedGoogle Scholar
  • 7 van der Putte SCJ. Normal and abnormal development of the anorectum. J Pediatr Surg 1986; 21 (05) 434-440
    CrossrefPubMedGoogle Scholar
  • 8 Kluth D, Hillen M, Lambrecht W. The principles of normal and abnormal hindgut development. J Pediatr Surg 1995; 30 (08) 1143-1147
    CrossrefPubMedGoogle Scholar
  • 9 Kluth D, Lambrecht W. Current concepts in the embryology of anorectal malformations. Semin Pediatr Surg 1997; 6 (04) 180-186
    PubMedGoogle Scholar
  • 10 Nievelstein RA, van der Werff JF, Verbeek FJ, Valk J, Vermeij-Keers C. Normal and abnormal embryonic development of the anorectum in human embryos. Teratology 1998; 57 (02) 70-78
    CrossrefPubMedGoogle Scholar
  • 11 Danforth CH. Developmental anomalies in a special strain of mice. Am J Anat 1930; 45: 275-287
    CrossrefPubMedGoogle Scholar
  • 12 Favre A, Briano S, Mazzola C. , et al. Anorectal malformations associated with enteric dysganglionosis in Danforth's short tail (Sd) mice. J Pediatr Surg 1999; 34 (12) 1818-1821
    CrossrefPubMedGoogle Scholar
  • 13 Lambrecht W, Lierse W. The internal sphincter in anorectal malformations: morphologic investigations in neonatal pigs. J Pediatr Surg 1987; 22 (12) 1160-1168
    CrossrefPubMedGoogle Scholar
  • 14 Hori T, Giuffra E, Andersson L, Ohkawa H. Mapping loci causing susceptibility to anal atresia in pigs, using a resource pedigree. J Pediatr Surg 2001; 36 (09) 1370-1374
    CrossrefPubMedGoogle Scholar
  • 15 Mesrobian HGJ, Sessions RP, Lloyd RA, Sulik KK. Cloacal and urogenital abnormalities induced by etretinate in mice. J Urol 1994; 152 (2, Pt 2): 675-678
    CrossrefPubMedGoogle Scholar
  • 16 Kubota Y, Shimotake T, Iwai N. Congenital anomalies in mice induced by etretinate. Eur J Pediatr Surg 2000; 10 (04) 248-251
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Khera KS. Ethylenethiourea: teratogenicity study in rats and rabbits. Teratology 1973; 7 (03) 243-252
    CrossrefPubMedGoogle Scholar
  • 18 Ruddick JA, Khera KS. Pattern of anomalies following single oral doses of ethylenethiourea to pregnant rats. Teratology 1975; 12 (03) 277-281
    CrossrefPubMedGoogle Scholar
  • 19 National Toxicology Program. Ethylene thiourea. Rep Carcinog 2011; 12: 191-194
    PubMedGoogle Scholar
  • 20 Hirai Y, Kuwabara N. Transplacentally induced anorectal malformations in rats. J Pediatr Surg 1990; 25 (07) 812-816
    CrossrefPubMedGoogle Scholar
  • 21 Qi BQ, Beasley SW, Frizelle FA. Clarification of the processes that lead to anorectal malformations in the ETU-induced rat model of imperforate anus. J Pediatr Surg 2002; 37 (09) 1305-1312
    CrossrefPubMedGoogle Scholar
  • 22 Qi BQ, Beasley SW, Arsic D. Abnormalities of the vertebral column and ribs associated with anorectal malformations. Pediatr Surg Int 2004; 20 (07) 529-533
    PubMedGoogle Scholar
  • 23 Zhang SW, Bai YZ, Zhang SC. , et al. Embryonic development of the striated muscle complex in rats with anorectal malformations. J Pediatr Surg 2008; 43 (08) 1452-1458
    CrossrefPubMedGoogle Scholar
  • 24 Dawrant MJ, Giles S, Bannigan J, Puri P. Adriamycin produces a reproducible teratogenic model of vertebral, anal, cardiovascular, tracheal, esophageal, renal, and limb anomalies in the mouse. J Pediatr Surg 2007; 42 (10) 1652-1658
    CrossrefPubMedGoogle Scholar
  • 25 Sato H, Hajduk P, Furuta S. , et al. Effect of abnormal notochord delamination on hindgut development in the Adriamycin mouse model. Pediatr Surg Int 2013; 29 (11) 1209-1216
    CrossrefPubMedGoogle Scholar
  • 26 Gillick J, Mooney E, Giles S, Bannigan J, Puri P. Notochord anomalies in the adriamycin rat model: a morphologic and molecular basis for the VACTERL association. J Pediatr Surg 2003; 38 (03) 469-473
    CrossrefPubMedGoogle Scholar
  • 27 Macedo M, Martins JL, Meyer KF. Evaluation of an experimental model for anorectal anomalies induced by ethylenethiourea. Acta Cir Bras 2007; 22 (02) 130-136
    CrossrefPubMedGoogle Scholar
  • 28 Macedo M, Martins JL, Meyer KF, Soares IC. Study of the density of ganglion cells in the terminal bowel of rats with anorectal malformations. Acta Cir Bras 2007; 22 (06) 441-445
    CrossrefPubMedGoogle Scholar
  • 29 Macedo M, Martins JL, Meyer KF, Soares IC. Study of density of interstitial cells of cajal in the terminal intestine of rats with anorectal malformation. Eur J Pediatr Surg 2008; 18 (02) 75-79
    Article in Thieme ConnectPubMedGoogle Scholar
  • 30 Lemos SPP, Martins JL, Lemos PVRB, Silva SR, Santos FL, Silva Júnior VA. Abnormalities of digestive tract innervation in rat fetus treated with ethylenethiourea. Acta Cir Bras 2012; 27 (03) 244-250
    CrossrefPubMedGoogle Scholar
  • 31 Wolff T, Witkop CT, Miller T. , et al; U.S. Preventive Services Task Force. Folic acid for the prevention of neural tube defects: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2009; 150 (09) 626-631
    PubMedGoogle Scholar
  • 32 Faria DJF, Simões MdeJ, Martins JL. Is it possible folic acid reduce anorectal malformations ethylenethiourea induced in rats?. Acta Cir Bras 2015; 30 (08) 517-522
    CrossrefPubMedGoogle Scholar
  • 33 Faria DJF, Simões MdeJ, Teixeira LC, Faria AT, Cintra ÁE, Martins JL. Effect of folic acid in a modified experimental model of anorectal malformations adriamycin-induced in rats. Acta Cir Bras 2016; 31 (01) 22-27
    CrossrefPubMedGoogle Scholar
  • 34 Peña A, Devries PA. Posterior sagittal anorectoplasty: important technical considerations and new applications. J Pediatr Surg 1982; 17 (06) 796-811
    CrossrefPubMedGoogle Scholar
  • 35 Levitt MA, Peña A. Cloacal malformations: lessons learned from 490 cases. Semin Pediatr Surg 2010; 19 (02) 128-138
    CrossrefPubMedGoogle Scholar
  • 36 Gupta A, Bischoff A, Peña A, Runck LA, Guasch G. The great divide: septation and malformation of the cloaca, and its implications for surgeons. Pediatr Surg Int 2014; 30 (11) 1089-1095
    CrossrefPubMedGoogle Scholar