Abnormal patterns of ossification in foot bones of rat fetuses induced by cyclophosphamide

Abstract

A series of 346 hind limbs from rat fetuses was collected on the 21st day of gestation (D 21) and 432 on the 23rd day (D 23) after a single maternal administration of cyclophosphamide (8-20 mg/kg) on D 12-14 of gestation. One hundred control fetuses were also collected. Ossification centers of the feet were studied after staining with alizarin red S. The patterns of ossification deviated from normal in 96-98% of limbs treated on the 13th day of gestation. The appearance of various centers on the 23rd day of gestation that had been seen to be suppressed by the teratogenic effect of cyclophosphamide on the 21st day, resulted in a significantly higher (P<0.01) number of patterns in the D 23 group (27 patterns) as compared to the D 21 group (8 patterns). The disorderly manner in which various centers of ossification appeared during further skeletal maturation indicated mesenchymal damage by the drug as well as suppression of ossification. The teratogenic effect was most marked in those injected on D 13, and least marked in those injected on D 12, which conforms with the normal variability of hind limb development during these periods.