Embryology of anorectal malformations

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Today, the normal and abnormal development of the hindgut is still a matter of speculation. However, as the result of recent studies in appropriate animal models, most embryologic events that finally lead to abnormal hindgut development are better known than in the past: (1) the process of maldevelopment starts in early embryonic stages; (2) the cloacal membrane is always too short in its dorsal part, thus, the dorsal cloaca is missing; and (3) as a result, the hindgut remains attached to the sinus urogenitalis, forming the recto-urethral fistula. In the past, an impaired process of septation was believed to be the main cause of abnormal hindgut development. In contrast to this, our results indicate that the development of the septum is more passive than active. Furthermore, the results of our studies in normal and abnormal development indicate that (1) the embryonic cloaca never passes through a stage that is similar to any form of anorectal malformation in neonates, including the so-called “cloacas” in female embryos, and (2) to explain abnormal development, studies in abnormal embryos are mandatory.

Section snippets

The etiology of anorectal malformations

The etiology of ARMs is still unclear. Most researchers assume that its etiology is multifactorial. However, recently a number of animal models has been deployed to study the background of ARM. In these models genetic as well as environmental factors were identified.

  • 1

    The SD-mouse model: these mice, first bred by Danforth,8 prominently feature a short tail and therefore also are known as “Danforth's short tail mice.”9

  • 2

    The pig model: another famous model for abnormal hindgut development is the pig.

Normal embryology of the hindgut

The normal embryology of the hindgut always has been a matter of debate because observations made in normal embryos should not only explain the normal embryology but also its abnormal counterpart. As a result, the explanation of normal embryology was always done with abnormal development in mind. Two major theories exist to explain the differentiation of the hindgut into the urogenital (ventral) and anorectal (dorsal) part:

  • 1

    The theory of the septation of the cloaca; and

  • 2

    The theory of the

Nomenclature

It must be kept in mind that the term “cloaca” is used to describe not only a transitional organ system in human embryos but also a congenital anomaly and a normal organ in birds. This can lead to the false conclusion that the morphology of these 3 entities is similar. This is not the case. Despite the same name, embryonic cloacas are completely different morphologically from cloacas in females with ARM and in birds. The main difference is the presence/absence of the area of the future anal

Abnormal cloacal development

Until recently,35 the embryology of abnormal hindgut development was generally a matter of speculation. Progress in this field has been hampered by lack of appropriate animal models that would permit systematic embryological studies in a sufficient series of malformed embryos. In 1940, a mutant of the normal house mouse, the SD-mutant, had been described by Dunn et al.36 These mice, first bred by Danforth,8 prominently feature a short tail and therefore also are known as “Danforth's short tail

Conclusions

Traditionally, the normal differentiation of the cloaca into the dorsal anorectum and the ventral urogenital tract is attributable to the proper process of septation by the so-called urorectal septum.38 However, when we used SEM in our study, we noted that neither lateral ridges nor signs of fusing lateral wall components could be discerned. Therefore, clear proof of this process of septation is still missing. It is more likely that a normal-looking septum is the result of normal cloacal

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      It is commonly believed that the urorectal septum (URS) divides the embryonic cloaca into a ventral urogenital sinus and separate dorsal hindgut,2-6 and the spectrum of anomalies seen clinically likely results from the timing of some kind of developmental arrest.7 However, the mechanism of cloacal septation has been debated with the emphasis shifting to the cloacal membrane (CM) playing a more important role during development of the anorectum8-10 and the mechanism for changes in embryonic anorectal morphology regarded as being the result of embryonic cell differentiation, cell proliferation, and apoptosis.11,12 The definitive cause of ARMs is unknown, but one third of ARMs are isolated and the remainder associated with other congenital urogenital, cardiovascular, skeletomuscular and gastrointestinal tract anomalies.13,14

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    Supported in part by Deutsche Forschungsgemeinschaft, Grant Number KL 596/1, Hamburg Werner-Otto-Stiftung.

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