The great divide: septation and malformation of the cloaca, and its implications for surgeons

Abstract

The anorectal and urogenital systems arise from a common embryonic structure termed cloaca. Subsequent development leads to the division/septation of the cloaca into the urethra, urinary bladder, vagina, anal canal, and rectum. Defective cloacal development and the resulting anorectal and urogenital malformations are some of the most severe congenital anomalies encountered in children. In the most severe form in females, the rectum, vagina, and urethra fail to develop separately and drain via a single common channel known as a cloaca into the perineum. In this review, we summarize our current knowledge of embryonic cloaca development and malformation, and compare them to what has already been described in the literature. We describe the use of mouse models of cloaca malformation to understand which signaling pathways and cellular mechanisms are involved in the process of normal cloaca development. We also discuss the embryological correlation of the epithelial and stromal histology found in step sections of the common channel in 14 human cloaca malformations. Finally, we highlight the significance of these findings, compare them to prior studies, and discuss their implications for the pediatric surgeons. Understanding and identifying the molecular basis for cloaca malformation could provide foundation for tissue engineering efforts that in the future would reflect better surgical reconstruction and improved quality of life for patients.

Fig. 1. Cloacal septation in human

(A) At 5 weeks gestation the cloaca is not separated. (B) At 6 week, the cloaca is divided into the urogenital sinus and the hindgut. (C) By 12 weeks, the 3 openings (anus, vagina and urethra), denoted by the black arrows, are formed. cl: cloaca; ugs: urogenital sinus; urs: urorectal septum; hg: hindgut; ur: urethra.

Fig. 2. Analysis of different regions of the common channel found in cloaca malformation

In cloaca malformation, the urethra, vagina and rectum fail to separate, and drain via a single common channel. Three areas shown by the squares labelled “a”, “b” and “c” have been analyzed histologically and molecularly. Area “a” is closest to the vagina, area “b” is closest to the rectum and area “c” is the most distal part of the common channel.