Cloacal malformations are characterized by the confluence of the lower urinary tract, the female reproductive tract, and the rectum to create a common channel with a single opening on the perineum. The presence of a cloaca is a normal phase of early human embryological development. Between the 4^th and 7^th weeks of gestation, the cloaca undergoes subdivision to form the hindgut and urogenital sinus. Failure of this process results in the congenital anomaly termed persistent cloaca (PC). The term urorectal septum malformation sequence (URSMS) is also used to describe this anomaly. The classic description of this process which is still cited in many standard textbooks dates from the 19^th century. However, this has been increasingly called into question by the findings of studies using modern scientific methodology. Urogenital sinus anomalies are defined by the confluence of the urethra and vagina to form a common channel of varying length with a single perineal opening. In this condition, the anorectal canal opens separately on the perineum. The presence of a urogenital sinus represents a transient phase of the normal development of the lower genital tract in the female fetus. However, the form of urogenital sinus most commonly encountered in the developed world is a feature of disordered sexual differentiation and does not arise simply from the persistence of the anatomical structure which is a feature of normal fetal development.
Cloaca/embryology* ; Female ; Humans ; Urogenital Abnormalities/embryology* ; Vagina/embryology*

OBJECTIVEIn the normal embryonic development of anorectum, apoptosis plays an important role. To explore the role of apoptosis in anorectal malformations (ARM), this study investigated cell apoptosis during the cloacal embryonic development in ARM embryos.

METHODSARM embryos were induced by intragastric administration of ethylenethiourea (125 mg/kg) for pregnant rats on embryonic day 10 (E10). The distribution of apoptotic cells in the cloaca was ascertained by hematoxylin and eosin and TUNEL staining in the normal control embryos (n=102) and ARM embryos (n=147) on E13, E13.5, E14, E15 and E16.

RESULTSOn E13, apoptotic cells were detected in the urorectal septum of rat embryos in the control group. With the development of embryos, the number of apoptotic cells in the mesenchyme of urorectal septum gradually increased and a large number of apoptotic cells were seen in the dorsal rectal mesenchyme. On E14, apoptotic cells appeared at the terminal rectum and the dorsal cloacal membrane. On E15, the urorectal septum fused with the cloacal membrane and apoptotic cells in the urorectal septum mesenchyme continuously extended down to the fusion region. Compared with the control group, apoptotic cells in the urorectal septum, the dorsal rectal mesenchyme and the cloacal membrane of the ARM rat embryos were significantly reduced during the embryonic development. The development of the urorectal septum was delayed and it did not fuse with the cloacal membrane in ARM embryos.

CONCLUSIONSDuring the embryonic development of cloaca, abnormal apoptosis in the urorectal septum, the dorsal rectal mesenchyme and the cloacal membrane may be one of the reasons for anorectal malformations. The proper regulation of cell apoptosis may be one of the key mechanisms for normal development of anorectum in the embryonic stage.

Anal Canal ; abnormalities ; Animals ; Apoptosis ; Cloaca ; embryology ; pathology ; Embryonic Development ; Female ; Pregnancy ; Rats ; Rats, Wistar ; Rectum ; abnormalities