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 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 fourteen 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.

Maternal intake of one-carbon metabolism-related B vitamins and anorectal malformations in the Japan Environment and Children’s Study

“…This association, however, was only observed in early pregnancy, not in mid-late pregnancy. Given that the embryonic period (the first 8 weeks) is important in terms of the developmental origins of ARM (36) , the observed tendency towards an inverse association with combined B vitamin intake in early pregnancy did not conflict with our hypothesis. The JECS includes one of the largest birth cohorts in the world (21) .…”

Systematic stereoscopic analyses for cloacal development: The origin of anorectal malformations

“…It has been described in medical textbooks that the urogenital sinus (UGS; ventral) and the rectum (dorsal) are formed as a result of cloacal separation 1 2 . Defective cloacal development and resultant anorectal and urogenital malformations are some of the most severe congenital anomalies in humans 3 . Anorectal malformations (ARMs) represent a common pathology that occurs in approximately 2–5 per 10,000 live births 4 .…”

“…These signaling molecules are suggested to regulate the development of several organs through epithelial-mesenchymal interactions 20 21 22 23 24 . In addition, analyses of human fetuses suggest that the spectrum of anomalies associated with cloaca malformation likely results from the timing of embryological developmental arrest 3 25 . Although these causative factors for ARMs have been pointed out, the pathogenic mechanisms remain unclear.…”

Mutations of MYH14 are associated to anorectal malformations with recto‐perineal fistulas in a small subset of Chinese population

“…Despite the unclear mechanism of anorectal development, the mainstream idea is that the embryonic cloaca division plays an important part in the formation of digestive and urinary tracts and cloaca malformations may lead to anorectal and urogenital abnormalities . During cloacal division of mouse embryos, drastic alteration of the cloacal morphology was observed from E10.5 onward, which reminds us of the temporal expression of NMHC IIC.…”