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Event: 1970

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

transposition of the great arteries

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
Transposition of the great arteries
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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
RALDH2 and cardiovascular developmental defects AdverseOutcome Gina Mennen (send email) Open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Sex Applicability

An indication of the the relevant sex for this KE. More help

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

The pharyngeal arches include the pharyngeal arteries, which are responsible for correct vascular development. There are six pharyngeal arteries from which the third, fourth and sixth artery will become part of the great vessels. The third pharyngeal arteries become the carotid artery, The right fourth artery becomes the proximal part of the subclavian artery, while the left fourth pharyngeal artery will form the aortic arch. The right sixth pharyngeal artery will form the proximal part of the pulmonary arteries and the left artery will become the ductus arteriosus. Stressors related to this AO showed relationships to the ATRA pathway. Vitamin A deficiency in embryos results in heart developmental defects such as septal defects, abnormalities to the inflow and outflow tract, aortic arch abnormalities and coronary malformations in quail and rat (Dersch & Zile, 1993; Heine et al., 1985; Wilson & Warkany, 1949, 1950).

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

Regulatory Significance of the Adverse Outcome

An AO is a specialised KE that represents the end (an adverse outcome of regulatory significance) of an AOP. More help


List of the literature that was cited for this KE description. More help

Cipollone, D., Amati, F., Carsetti, R., Placidi, S., Biancolella, M., D’Amati, G., Novelli, G., Siracusa, G., & Marino, B. (2006). A multiple retinoic acid antagonist induces conotruncal anomalies, including transposition of the great arteries, in mice. Cardiovascular Pathology : The Official Journal of the Society for Cardiovascular Pathology, 15(4), 194–202.

Dersch, H., & Zile, M. H. (1993). Induction of normal cardiovascular development in the vitamin A-deprived quail embryo by natural retinoids. Developmental Biology, 160(2), 424–433.

Fujino, H., Nakagawa, M., Nishijima, S., Okamoto, N., Hanato, T., Watanabe, N., Shirai, T., Kamiya, H., & Takeuchi, Y. (2005). Morphological differences in cardiovascular anomalies induced by bis-diamine between Sprague-Dawley and Wistar rats. Congenital Anomalies, 45(2), 52–58.

Heine, U. I., Roberts, A. B., Munoz, E. F., Roche, N. S., & Sporn, M. B. (1985). Effects of retinoid deficiency on the development of the heart and vascular system of the quail embryo. Virchows Archiv. B, Cell Pathology Including Molecular Pathology, 50(2), 135–152.

Kise, K., Nakagawa, M., Okamoto, N., Hanato, T., Watanabe, N., Nishijima, S., Fujino, H., Takeuchi, Y., & Shiraishi, I. (2005). Teratogenic effects of bis-diamine on the developing cardiac conduction system. Birth Defects Research Part A - Clinical and Molecular Teratology, 73(8), 547–554.

Kuribayashi, T., & Roberts, W. C. (1993). Tetralogy of fallot, truncus arteriosus, abnormal myocardial architecture and anomalies of the aortic arch system induced by bis-diamine in rat fetuses. Journal of the American College of Cardiology, 21(3), 768–776.

Nishijima, S., Nakagawa, M., Fujino, H., Hanato, T., Okamoto, N., & Shimada, M. (2000). Teratogenic effects of bis-diamine on early embryonic rat heart: An in vitro study. Teratology, 62(2), 115–122.<115::aid-tera8>;2-%23

Okamoto, N., Nakagawa, M., Fujino, H., Nishijima, S., Hanato, T., Narita, T., Takeuchi, Y., & Imanaka-Yoshida, K. (2004). Teratogenic Effects of Bis-diamine on the Developing Myocardium. Birth Defects Research Part A - Clinical and Molecular Teratology, 70(3), 132–141.

Okishima, T., Takamura, K., Matsuoka, Y., Ohdo, S., & Hayakawa, K. (1992). Cardiovascular anomalies in chick embryos produced by bis‐diamine in dimethylsulfoxide. Teratology, 45(2), 155–162.

Tasaka, H., Takenaka, H., Okamoto, N., Onitsuka, T., Koga, Y., & Hamada, M. (1991). Abnormal development of cardiovascular systems in rat embryos treated with bisdiamine. Teratology, 43(3), 191–200.

Wang, S., Huang, W., Castillo, H. A., Kane, M. A., Xavier-Neto, J., Trainor, P. A., & Moise, A. R. (2018). Alterations in retinoic acid signaling affect the development of the mouse coronary vasculature. Developmental Dynamics, 247(8), 976–991.

Wilson, J. G., & Warkany, J. (1949). Aortic-arch and cardiac anomalies in the offspring of vitamin A deficient rats. The American Journal of Anatomy, 85(1), 113–155.

Wilson, J. G., & Warkany, J. (1950). Cardiac and aortic arch anomalies in the offspring of vitamin A deficient rats correlated with similar human anomalies. Pediatrics, 5(4), 708–725.