The morphology of various types of cell death in prenatal tissues

Abstract The morphology of physiological cell death and of necroses caused by treatment with various embryotoxic substances (cyclophosphamide, actinomycin D, vitamin A, vincristine, 6‐aminonicotinamide, 6‐mercaptopurine) and Mg deficiency were studied electron microscopically in rat and mouse embryos and fetuses. Three types of necroses were distinguished in control tissues. (1) Condensation and fragmentation of single cells undergoing phagocytosis, with lysosomal disintegration of the fragments in neighboring cells. (2) Primary formation of lysosomes in dying cells, with activation and subsequent destruction and phagocytosis of the fragments by neighboring cells. This type of cell death in most instances was found during destruction of organs and large cell units. (3) Disintegration of cells into fragments, which were optically no longer detectable, without involvement of the lysosomal system, e.g., in embryonic and epiphyseal cartilage before ossification. In cases of embryolethal toxic agents, e.g., Mg deficiency, cell necroses of large areas prevailed, which were characterized by typical pyknoses (rough, dense chromatin) and lack of lysosomes. In the case of teratogenic effects, however, substances that disturb replication, transcription, and translation (cyclophosphamide, actinomycin D, 6‐mercaptopurine) caused an increase in the number of necroses of type 1. It can, therefore, be assumed that under these conditions similar processes take place in physiological and experimentally induced necroses. After administration of vitamin A, labilization of lysosomes and necroses of type 2 were observed.