Malformations of the axial skeleton in cranioschisis aperta and exencephaly in rat fetuses induced after neural tube closure.

Single doses of cyclophosphamide were administered (IP) to groups of Wistar rats, on different days of gestation after neural tube closure (days 12-15) and fetuses were collected on day 20. A very large number of the fetuses treated during days 12-14 exhibited cranioschisis and exencephaly. Ethanol fixed, alizarin red stained specimens were observed for axial skeletal abnormalities. The exencephalic ones lacked ossified skulls. The basicranial bones were either under ossified or had undergone extensive fusion resulting in reduction in cranial volume. The basicraniovertebral angle was obtuse. The vertebral bodies and arches showed varying degrees of hypoplasia, fusion and/or agenesis. The development of ribs and sternebrae was also extensively affected. Treatment on day 15 did not induce exencephaly but the axial skeleton was hypoplastic. Wavy ribs were a remarkable feature of these fetuses. All exencephalic fetuses had subcutaneous haemorrhages; many of them were obviously oedematous. These data indicate that the susceptible period for induction of these anomalies does not stop at neuropore closure.