Effects of in utero exposure to cyclophosphamide in mice. I. Pregnancy outcome and observations of offspring during early postnatal life.

ABSTRACT

Swiss-Webster mice treated orally with cyclophosphamide (Cy) (1, 2.5 or 5 mg/kg) once daily on gestational days 6 through 18 gave birth to pups which appeared to be normal and the majority of which survived to adulthood. The maternal treatment resulted in reduced mean pup weight at birth and increased cumulative pup mortality. On the other hand, pregnancy outcome and mean pup body, spleen and thymus weights, when measured at 4 weeks of age, were within the control ranges. Similarly, hematological profiles, serum immunoglobulin (IgG, IgM) levels and histology of the lymphoid tissue (spleen and thymus), assessed at 4 weeks of age, were not affected by the maternal treatment. Treatment with 7.5 mg/kg Cy not only resulted in reduced litter size but also increased the cumulative pup mortality. In addition, with this dose, histopathological changes were observed in the thymus in 2-and 3-week old pups. The morphology of the thymus in 4-week old pups was unremarkable. At the dose of 10 mg/kg no live births were recorded.