Responses of the developing fetal nervous system to roentgen irradiation.

Abstract

The embryo and the fetus together represent the most dynamic period in the life of any organism, during which there is a constantly changing mosaic of developmental activity. In addition there is accelerating growth from the relative simplicity of the single-celled zygote to the multimillion-cell organism. Any insult to any part, or to the whole, during this phase may result in abnormalities which cannot be produced at any subsequent period in the life of the organism. Ionizing radiations constitute a very powerful means of interfering with any biological process, and their effects are more marked and even of different kinds when the embryo or fetus is exposed than in postnatal stages—exaggerated because of the high radiosensitivity during any developmental activity and different because there is interference with organogeny. Developmental abnormalities can be produced only by irradiation during the prenatal stages. In contrast to the adult organism, there is no uniformity in the reaction of the embryo or fetus from moment to moment, due to the constantly changing structures and dynamic activity. It is therefore impossible to predict, on any quantitative basis, the teratogenic effect of any exposure to ionizing radiations. This unpredictability is not to be confused with normal biological variability, which is probably primarily of genetic origin, but rather to be attributed to other factors peculiar to prenatal development. Nevertheless, certain abnormalities are more likely to occur following even low-level irradiation at specified periods of development; yet it is possible to produce some of the same changes at later stages but only by higher levels of irradiation. It is probable that low levels of exposure which do not cause teratisms may nevertheless bring about ultimate subtle sequelae detectable only by physiological or psychological tests. If it be assumed from these statements that we do not know the low-level exposure of the embryo and fetus which has no effect, that assumption is indeed correct. The purpose of this paper is to demonstrate that at the morphological level the embryo or fetus as a whole has remarkable powers of resilience and repair, following x-irradiation insult, which can result in an organism topographically quite normal but reduced in size or function. The nervous system integrates and permeates every part of the organism; from about the twentieth day in the human embryo, and continuously until some weeks after birth, there are embryonic differentiating neuroblasts in increasing abundance, developing from their neurectodermal precursors in association with each of the various organ systems. Neuroblasts are the intermediate stage between the primitive precursor and the ultimate neurone and are now believed to be the most radiosensitive of all cells, rarely surviving an exposure of 40 r.