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Effects of thalidomide on F gf8, B mp4 and H oxa11 expression in the limb bud in K bl: JW rabbit embryos
Author(s) -
Kawamura Yoshinori,
Yamashita Teruyoshi,
Yamauchi Toshiaki,
Matsumoto Kiyoshi,
Sato Keiichiro
Publication year - 2014
Publication title -
congenital anomalies
Language(s) - English
Resource type - Journals
eISSN - 1741-4520
pISSN - 0914-3505
DOI - 10.1111/cga.12046
Subject(s) - forelimb , limb bud , fgf8 , embryo , apical ectodermal ridge , hindlimb , anatomy , biology , teratology , thalidomide , limb development , in situ hybridization , endocrinology , embryogenesis , medicine , pregnancy , fetus , gene expression , fibroblast growth factor , microbiology and biotechnology , genetics , receptor , gene , ectoderm , multiple myeloma
Thalidomide ( TM ) induces limb defects in humans and some animal species including rabbits. Although the mechanism of TM ‐induced limb defects has been investigated for a long period, the limb development‐related genes expressions have not been vigorously characterized in rabbits. In this study, we investigated the F gf8, B mp4 and H oxa11 expressions in TM ‐treated JW rabbit embryos on gestation days ( GD s) 10, 11 and 12 by whole mount in situ hybridization. On GD s 10 and 11, growth retardation of the embryo was induced by TM treatment. The F gf8 expression lengths on GD s 10 and 11 in the forelimb bud were significantly or tended to be decreased in the TM ‐treated embryos, which was correlated to the growth retardation and was not considered to be directly relevant to the teratogenic effect of TM in the forelimb. The TM ‐induced characteristic changes in the expression pattern of H oxa11 and B mp4 on GD s 10 and/or 11 were not noted. On GD 12, TM ‐induced growth retardation was not noted and the F gf8 and B mp4 expressions were not changed. On the contrary, H oxa11 expression was narrowed at the anterior region, which was located on the radial side, and was not changed at the middle and posterior regions in the forelimb bud and in all regions in the hindlimb bud. Because the radius malformations were induced by TM treatment, we concluded the decrease in the H oxa11 expression was related to the TM ‐induced limb defects and can be a good marker for early prediction of the teratogenic effect of TM .