Transplacentally induced anorectal malformations in rats

Abstract

Twenty-eight pregnant rats (Wistar-Imamichi) on the 11th gestation day were treated with a single intragastric administration of ethylenethiourea (ETU) of 100, 125, 150, and 200 mg/kg body weight, and received cesarean section on the 20th gestation day. No dam died following the ETU treatment. In these transplacentally treated rat fetuses, various types of externally visible malformations were frequently observed; absent or kinked short tail in 100% and spina bifida or myeloschisis in 48.6% to 86.8%. The incidences of these anomalies were significantly higher in males than females. The fetuses were fixed in Bouin's solution and embedded in paraffin, and the step-serial section were sagittally prepared. Then they were stained with phosphotungstic acid hematoxylin for the light microscopic examination. In a preparation of just midsagittal section, malformations of rectum and anus were investigated. The results were as follows: (1) the most appropriate dose of ETU might be 125 mg/kg, body weight of dam, which was suggested by number of the fetuses, prenatal development of the fetuses and incidences of externally visible anomalies in the fetuses; (2) various types of anorectal anomalies, including rectourethral fistula, rectocloacal fistula, covered anus-complete, anoperineal fistula, and anal membrane stenosis, were induced; (3) the incidence of anorectal anomalies was significantly higher in males than females; (4) in every type of anorectal anomalies, inner circular layer of smooth muscle was hypertrophied at the rectum end, which seemed to be considered as the internal sphincter muscle; and (5) the external sphincter muscle complex was hypoplastic in the high deformity fetuses associated with sacrococcygeal anomaly.