DEVELOPMENTAL TOXICOLOGY

This book contains many examples of abnormal development due to either intrinsic defects in gene expression or epigenetic modifications of normal gene expression. Chapter 16, in particular, is concerned with recognized teratogenic derangements of sexual differentiation resulting from exposure to hormonally active xenobiotics. The present chapter outlines the principles underlying mutagenesis, teratogenesis and delayed development. Specific biochemical and physiological mechanisms and common developmental disturbances associated with nicotine, ethanol and caffeine consumption are also examined. It has been repeatedly emphasized that epigenetic factors can, by influencing the activity of genes, impinge on the differentiating oocyte or sperm and modify the identity of the future conceptus. Genomic or parental imprinting during gametogenesis which, at syngamy, begins to direct the normal development of the conceptus’ unique potential is a special case of epigenetic influence (Chapter 8). Teratology, on the other hand, is the science which deals with biological, genetic, biochemical, and behavioural aspects of maldirected development and spans the period from germ cell differentiation to the termination of functional development in the postpartum individual. Behavioural teratologogy refers to long-term effects on behaviour and psychological development. For example, infants prenatally exposed to substances like ethanol, opiates, various catecholamines and caffeine may experience neonatal withdrawal symptoms and neurobehavioural impairment such as hyperactivity, shortened attention span, co-ordination problems and specific learning difficulties.

The early stages of mammalian differentiation are times of greatest development flexibility. A robust genetic constitution may be able to repair mutational damage, although major defects are likely to cause spontaneous abortion or remain unrestored.