Experimental studies on congenital malformations

Abstract

A survey of the literature reveals that there are approximately 60 methods whereby congenital malformations have been produced in laboratory animals. These were grouped into several categories as follows: physical agents, nutritional deficiencies, growth and metabolic inhibitors, infectious agents, endocrine states, and a miscellaneous group of chemicals and drugs that had little in common except their teratogenicity. A representative list of agents that failed to cause malformations was also presented. After careful consideration of the available information it was possible to formulate five general principles that seem to be applicable to most situations in experimental teratology. (1) The susceptibility of an embryo depends upon the developmental stage at which a teratogenic agent is applied. (2) Each teratogenic agent appears to act in a specific way on a particular aspect of cellular metabolism. (3) The genotype of the animal influences to a greater or lesser degree the reaction to a teratogenic agent. (4) Agents that cause malformations also cause a rise in embryonic mortality. (5) Teratogenic agents may have little or no deleterious action on the maternal organism. Although present knowledge of the mechanisms of teratogenic action is meager, there are ample indications that several different pathways of action exist. Regardless of how it may be mediated, the ultimate action of all teratogens seems to be to produce either cell death or an alteration in the rate of cell growth (mitosis).