Histological study of timing and embryology of notochordal abnormalities in rat exposed in utero to Doxorubicin

Experimental Doxorubicin-exposure in utero is correlated with foetal oesophageal atresia, tracheo-oesophageal fistula, axial alterations. While gastrointestinal and respiratory defects have been largely investigated, only sporadic data have been published to date on notochordal and vertebral defects. The aim of this work was the study of the genesis of chordal and vertebral abnormalities in rat embryos and foetuses exposed to Doxorubicin and the study of their correlation with oesophageal and tracheal defects. For this purpose, pregnant rats were i.p. injected with saline (control) or with 4 mg/Kg b.w. Doxorubicin on days 9.5 and 10.5 of gestation. Embryos and foetuses were morphologically analysed on days 10.5-15 and 16, 18, 20 of gestation respectively, fixed in formaldehyde and histologically processed. Slides were routinely stained with haematoxylin-eosin (11-15 days post coitum embryos and all foetuses) or specifically stained with aniline blue for the staining of basal laminae (10.5 days post coitum embryos). Moreover, some foetuses at term (20 days post coitum) were processed for bone and cartilage staining. The data obtained in the present work confirm the specificity of Doxorubicin in inducing gastro-intestinal and tracheal defects, describe the genesis of these defects step by step, describe the type and the genesis of notochordal abnormalities and their fate and exclude the role of Doxorubicin in inducing axial skeletal malformations.