Development of the human tail bud and splanchnic mesenchyme.

The purpose of this paper was to shed some light on anorectal development from a viewpoint of the tail bud and splanchnic mesenchyme for better understanding of the morphogenesis of the human anorectum. Human embryos ranging from Carnegie stage 11 to 23 (CS 11 to 23) were adopted in this study. Seventeen embryos preserved at the Congenital Anomaly Research Center of Kyoto University Graduate School of Medicine were histologically examined. The cloaca, extending caudally to the hindgut, was dramatically enlarged, particularly both its dorsal portion and membrane, that is, the cloacal membrane resulting from the development of the tailgut derived from the tail bud. The splanchnic mesenchyme surrounding the hindgut was spread out in the direction of the urorectal septum ventrally, suggesting that it participated in the formation of the septum. No fusion of the urorectal septum and the cloacal membrane was found. The splanchnic mesenchyme proliferated and developed into smooth muscle (circular and longitudinal) layers from cranial to caudal along the hindgut. The tail bud seems to cause both the adequate dilation of the dorsal cloaca and the elongation of the cloacal membrane; its dorsal portion in particular will be necessary for normal anorectal development. The splanchnic mesenchyme developed and descended toward the pectinate line and formed the internal sphincter muscle at the terminal bowel.

Development of the human Müllerian duct in the sexually undifferentiated stage.

An embryological explanation for the development of the Müllerian duct still poses a major challenge. The development of this duct was investigated systematically in human embryos. Seven embryos (Carnegie stages 18-23) were serially sectioned in the frontal, sagittal, and transversal planes at a thickness of 10 microm and stained with hematoxylin and eosin (H&E) for histological analysis. In all observed embryos, the caudal end of the Müllerian duct was found to be intimately connected to the Wolffian duct. The opening of the Müllerian duct to the coelomic cavity was formed as the result of an invagination of the coelomic epithelium at Carnegie stage 18. The duct grew independently from the invagination during stages 19-23. The fused duct (uterovaginal canal) bifurcated at the caudal portion at Carnegie stages 22 and 23. This is the first description of the caudal portion of the fused Müllerian ducts separating again and returning to each of the Wolffian ducts in human embryos.

Relationship of the fistulas to the rectum and genitourinary tract in mouse fetuses with high anorectal malformations induced by all-trans retinoic acid.

Since high anorectal malformations with fistulae in human embryos and fetuses of successive developmental stages have not been reported, the embryologic relationship between the rectal fistula (RF) and the genitourinary tract (GUT) in high anorectal agenesis (ARA) remains to be elucidated. This study investigates the developmental relationship between the RF and the GUT in male and female fetuses with high ARA using our established model for high ARA with fistula in mice. Pregnant mice received all-trans retinoic acid suspended in corn oil (5 mg/ml) 100 mg/kg i.p. on day 9 of pregnancy. All fetuses were removed from the uterus on a single day from days 12 to 18 of pregnancy. The caudal regions were analyzed histologically with hematoxylin and eosin staining. All fetuses examined had high ARA with fistula. On day 12 of pregnancy, an anomalous communication was seen between the urogenital sinus (UGS) and the rectum. In the affected female fetuses, on day 14 of pregnancy the paramesonephric (müllerian) ducts and müllerian tubercle were located above the rectocloacal fistula (RCF), and on day 18 of pregnancy the uterovaginal canal was located between the cloaca and the RCF. In the male fetuses, on day 14 of pregnancy the junction between the mesonephric (wolffian) duct and the UGS was located away from the junction between the rectum and the UGS. On day 18 of pregnancy the ejaculatory duct was located between the urinary bladder and the rectourethral fistula. The results of our experiment clearly show the embryologic relationship between the RF and the GUT with high ARA. The anomalous communication between the UGS and the rectum may interfere with normal caudal migration along the dorsal wall of the UGS at the junction between the UGS and the mesonephric or paramesonephric duct.