The Pathogenesis of Anorectal Malformation Induced by All‐Trans Retinoic Acid in Mice

Abstract

ABSTRACTThe pathogenesis of anorectal malformations has been discussed for more than 100 years, however, much remains to be elucidated. We studied the pathogenesis of high‐type anorectal malformations induced by all‐trans retinoic acid (all‐trans RA) in mice. Pregnant females were injected intraperitoneally once with all‐trans RA, suspended in corn oil (5 mg/ml), at a dose of 100 mg/kg on day 9 of pregnancy. The all‐trans RA‐treated females were killed on one of days 10 to 18 of pregnancy. All fetuses examined on day 18 of pregnancy following in utero exposure to all‐trans RA had anorectal malformations. In the affected male fetuses, the rectum was positioned away from the retroperitoneum toward the ventral side leading to the opening of the urethra just underneath the urinary bladder. Deficiency of the cloacal plate at the dorsal part was also observed in the affected embryos during days 10–11 of pregnancy. The cloacal plate is considered to bring the cloacal cavity to the anus, and thus the deficiency of the dorsal part may be the major cause of the hightype anorectal malformations.