Morphogenesis of the Hindlimb Digits and 5-FU induced Apoptotic Changes

Lee, Sang Bong; Chui, Song Biao; Cho, Keun Ja; Yang, Eun Jin; Park, Kyung Ran; Lee, Young Ho; Kim, Won Sik

Abstract

During the morphogenesis of the hindlimb and the digits of the rat, apoptosis has a crucial role to make their normal shape. In this study, apoptotic changes of the hindlimb from GD 13.5 to GD 17.5 were observed and compared with 5 -FU treated group to reveal the mechanism of teratogenic action of 5 -FU. The results were as follows; 1. The mean body weight of rat fetuses was decreased significantly in the 5 -FU treated group. 2. Congenital anomalies of the hindlimb digits were cleft foot, syndactyly and short digits, and the occurance rate of congenital anomalies was 58.1%, in which right -sided anomalies was 49.1% and left -sided anomalies was 18.9%. 3. Normal morphogenesis of the hindlimb digits was as follows; initially, hindlimb bud appeared at the lateral wall of lumbar somite on GD 10.5, grown as an elliptical mass proximodistally on GD 13.5, flattening and digital rays formation on GD 14.5, interdigital notches appeared on GD 15.5, interdigital spaces formation and interphalageal joints formation on GD 16.5, and deepening of interdigital spaces and elongation of digits on GD 17.5. 4. 5 -FU inhibited differentiation and growth of hindlimb bud initially, but its effect on development of hindlimb was disappeared after GD 15.5. According to the above results, it is considered that 5 -FU has an inhibitory effect on differentiation and growth of hindlimb of rat fetuses, and the TUNEL immunohistochemical method is much available to detect normal morphogenesis of an organ and to detect the mechanism of action of various teratogens.