The morphogenesis of hindbrain crowding associated with lumbosacral myeloschisis

The teratogenicity of ethylenethiourea (ETU) was investigated in Sprague-Dawley rats and Landrace pigs. Pregnant rats each received a single intragastric dose of ETU on a given day from day 8 to day 19 of gestation, and pregnant pigs were given a single dose of ETU from day 15 to day 19. Control animals received an ETU-free vehicle. The newborn pigs were all normal, whereas there were high incidences of specific types of congenital malformation of the central nervous and other systems in the rats. A high incidence of lumbosacral myeloschisis associated with hindbrain crowding was observed in rat fetuses exposed to ETU on day 11 of gestation. This abnormality is considered comparable to Chiari type II malformation associated with spinal dysraphism (Arnold-Chiari malformation) in humans. Morphogenetic fetuses were examined by light and scanning electron microscopy and interactive image analysis. At gestational days 12 and 13, the volume of the caudal end of the neural tube from the anterior border of the hindlimb bud to the most caudal portion of the fetus was significantly greater in ETU-exposed than in control rat embryos. Experimental rat embryos also exhibited disturbance in closure of the posterior neuropore, with extrusion of neural tissue through the opening. An apparently unrelated abnormality in ETU-exposed rat fetuses was underdevelopment of the cranium, leading to hindbrain crowding.(ABSTRACT TRUNCATED AT 250 WORDS)