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Morphological differences in cardiovascular anomalies induced by bis‐diamine between Sprague–Dawley and Wistar rats
Author(s) -
Fujino Hidetoshi,
Nakagawa Masao,
Nishijima Setsuko,
Okamoto Nobuhiko,
Hanato Takashi,
Watanabe Noriko,
Shirai Takeaki,
Kamiya Hiroshi,
Takeuchi Yoshihiro
Publication year - 2005
Publication title -
congenital anomalies
Language(s) - English
Resource type - Journals
eISSN - 1741-4520
pISSN - 0914-3505
DOI - 10.1111/j.1741-4520.2005.00063.x
Subject(s) - truncus arteriosus , neural crest , embryo , teratology , tetralogy of fallot , aortic arch , medicine , endocrinology , biology , aorta , anatomy , andrology , pathology , pregnancy , fetus , heart disease , microbiology and biotechnology , genetics
It is known that animals show different responses to the same teratogen between different strains. We examined cardiac malformations in Sprague–Dawley (SD) and Wistar rats induced by bis‐diamine, which produced conotruncal anomalies and aortic arch malformations in embryos when administered to the dams, to elucidate the morphological differences and pathogenesis in the two strains. Two hundred milligrams of bis‐diamine dissolved in 1% gum‐tragacanth was administered to pregnant rats on embryonic day (ED) 9.5, 10.5 and 11.5 in each strain. The embryos were removed on ED 20.5. External appearances, cardiovascular morphology and associated anomalies were examined under a dissecting microscope. An immunohistological study with an anti‐N‐CAM antibody, an excellent marker for neural crest cells, was performed on ED 12.5 embryos. Isolated aortic arch anomalies were common features of malformations induced by bis‐diamine in SD rats and intracardiac defects were found in a small number of the embryos. Wistar rats showed more serious cardiovascular anomalies, such as persistent truncus arteriosus and tetralogy of Fallot, especially when dams were treated on ED 10.5 and isolated arch anomalies were significantly less prevalent than in SD rats. Immunohistology demonstrated that there were fewer N‐CAM positive cells in the conotruncal region in Wistar rats than in SD rats. Bis‐diamine induced more critical cardiovascular malformations in Wistar rats because neural crest cells, which play an important role in conotruncal septation, were more extensively damaged. Different susceptibility to bis‐diamine and/or different time of neural crest cell emigration from the hindbrain might explain those morphological differences.