Morphologic and Immunologic effects in the rat after prenatal exposure to Cyclophosphamide

Abstract

Several teratogens have been shown to alter postnatal immune function after prenatal exposure. Until now, relatively little is known about the perinatal maturation of the immune system and about the effects of teratogens on this process. Therefore, further research is necessary into the field of immunoteratology and especially into immunological parameters that can be measured as part of teratogenicity testing protocols. Using the immunosuppressive cytostatic agent cyclophosphamide as a model compound, morphological and immunological parameters were studied in day-20 rat fetuses after a single exposure on day 11 or day 15 of gestation. Methods included evaluation of visceral and skeletal morphology. Furthermore, histology, immunohistochemistry and flow cytometry using specific antibodies were performed on thymus, liver and spleen. Treatment resulted in dose-dependent gross morphological malformations. In addition severe skeletal anomalies were observed, such as brachygnathia, wavy ribs and lordosis. In contrast, the immunological parameters tested revealed no differences between treated and control groups. These results suggest either a remarkable recovery of the immune system after treatment or that the developing immune system is not damaged by cyclophosphamide.<br>