Experimental limb dysmorphogenesis as a model of chemical injury response in undifferentiated embryonic tissues: a light and electron microscopical study.

A histopathological and ultrastructural analysis of the early stage of limb dysmorphogenesis from 1 hr to 48 hr, following citral administration is presented as a model for studying the reaction to injury of undifferentiated embryonic tissues. Early lesions such as cloudy swelling, hydropic degeneration, enlargement of the extracellular space and retraction of protoplasmic extensions were observed 1 hr after treatment, affecting both epiderm and mesenchyme of the limb. Few pyknotic cells were encountered during the early stages. Cell necrosis and autophagocytosis became more conspicuous at 12 hr post-injection. About the same time the first signs of healing were observed, charcterised by heterophagocytosis and return of mitotic activity. The epiderm being more differentiated, regenerates ad integrum and more rapidly than the mesenchyme. The evolution of these pathological events, which proceed in a spatio-temporal cascade, seem to reflect the pharmacokinetic gradient of the cell-teratogen interactions. The type of limb malformation will depend mainly on the extent of injury and/or healing of the mesenchymal mass, rather than on the injury and/or healing of the surface ectoderm. It is concluded that the reaction to chemical injury of undifferentiated tissues partially mimics the destructive and repair process in adult tissues, but differs in lacking some basic constituents such as oedema, monocyte exudation and granulation tissue formation.