Abnormal development of cardiovascular systems in rat embryos treated with bisdiamine

Abstract

Administration of N,N'-bis(dichloroacetyl)-1,8-octamethylenediamine, bisdiamine, in pregnant Donryu rats on day 10 of gestation induces a high incidence of cardiovascular anomalies in fetuses. Bisdiamine administration induced aplasia of the sixth aortic arch artery, with both the right and left primitive pulmonary arteries being directly linked to the truncus, and resulting in four types of malformation of pulmonary arteries (PAs). When two primitive PAs shared a single root, the consequence was either pulmonary trunk hypoplasia, as is seen in tetralogy of Fallot, or type I persistent truncus arteriosus (PTA) as classified by Collet and Edwards. When root portions of two PAs did not fuse, either type II or type III PTA resulted. In controls, the right dorsal aorta (DA) between the right seventh intersegmental artery (IA) and the site where both DAs fuse degenerated and the left aortic arch (AA) and the right subclavian artery (SA) were formed. Bisdiamine administration induced two additional types of vascular anomalies. In one of these, the right DA between the right 4AA and the right 7IA degenerated and a left AA accompanied by an aberrant right SA resulted. In the other type, the left DA between the left 4AA and the left 7IA degenerated and a right AA accompanied by an aberrant left SA resulted. These results indicate that administration of bisdiamine induces malformation in the great blood vessels by disturbing persistency and degeneration of aortic arch arteries and DAs.

HNK-1 expression pattern in normal and bis-diamine induced malformed developing rat heart: three dimensional reconstruction analysis using computer graphics

“…In the late embryonic stage, 3D reconstructed images of the bis-diamine-induced malformed hearts revealed the incomplete absorption of the sinus to the atrium as well as conotruncal anomalies such as pulmonary hypoplasia with overriding aorta and persistent truncus arteriosus, as in previous reports (Taleporos et al 1978;Kawamoto 1984;Tasaka et al 1991). These anomalies were accompanied by an abnormality of the atria, incomplete absorption of the sinus venosus and an extracardiac communication of both SVC and IVC in our experiment.…”

“…Administration of bis-diamine to pregnant rats induces conotruncal anomalies in the embryonic heart, and these anomalies are said to be caused by disturbance of the extracellular matrix or the migration of neural crest cells which are the precursors of the mesenchyme in the aorticopulmonary septum (Taleporos et al 1978;Kawamoto 1984;Tasaka et al 1991). There has been no report, however, concerning the changes of the conduction system in the heart with cardiovascular anomalies.…”

Topological changes of the human autonomic cardiac nervous system in individuals with a retroesophageal right subclavian artery: two case reports and a brief review

“…On the other hand, the retroesophageal right subclavian artery was formed from the right seventh intersegmental artery and a distal part of the right dorsal aorta after interrupting the proximal part, the third to seventh segments, of the right dorsal aorta Warkany 1949, 1950;Kitchell et al 1957;Okishima et al 1987;Sumida 1988;Tasaka et al 1991). In these arterial anomalous developments, recent progresses were also recognized (Bergwerff et al 1999;Molin et al 2002).…”

Alterations in retinoic acid signaling affect the development of the mouse coronary vasculature

“…WIN, having been briefly investigated as a potential male contraceptive (Heller et al, 1961), was shown to be a potent inducer of congenital heart defects including coronary defects, yet, the cause for such defects remains poorly understood (Oster et al, 1974; Kilburn et al, 1982; Binder, 1985; Tasaka et al, 1991; Ito et al, 1992; Okishima et al, 1992; Kuribayashi and Roberts, 1993; Jackson et al, 1995; Nishijima et al, 2000; Okamoto et al, 2004; Fujino et al, 2005; Kise et al, 2005; Hanato et al, 2011). We found that administration of WIN between E9.5 and E13.5 dramatically reduced the amount of RA and alters RA-signaling in developing mouse embryos and their hearts (Wang et al, 2018).…”