Micronucleated Erythrocytes in Peripheral Blood of Newborn Rabbits after Exposure to Cyclophosphamide during Pregnancy

There are ever increasing numbers of new chemicals and pharmaceutical products that have the potential to induce birth defects or to cause damage during the perinatal period in humans. Many genotoxic compounds possess teratogenic potential and induce the formation of micronuclei (MN). Objective: To demonstrate that the New Zealand rabbit may be a useful animal model for the evaluation of transplacental genotoxicity and potential teratogenicity of compounds by quantifying micronucleated erythrocytes (MNE) in the peripheral blood of newborn rabbits following maternal exposure. Method: For each dose, a single pregnant rabbit was injected daily on the 25th to 30th days of pregnancy with 1, 4, or 7 mg/kg cyclophosphamide (CP) with one pregnant rabbit being treated with sterile water as the control. Following the daily intramuscular administrations, a drop of blood was taken from six newborn rabbits from each female for microscopic analyses. Results: When compared with controls, significant differences (p < 0.002) were observed in the number of MNE and micronucleated polychromatic erythrocytes (MNPCE) from newborns of females treated with 4 or 7 mg/kg CP, but not from newborns exposed to 1 mg/kg CP. No cytotoxic effects were observed after the treatments. We concluded that the presence of MNE in newborn rabbits suggests that the rabbit may be useful animal model for the detection and prevention of transplacental genotoxicity and/or potential teratogenicity of compounds in the peripheral blood of newborn rabbits following maternal exposure.