Controlled death of cells is as much a part of embryonal development as is cell proliferation and differentiation. This cell suicide is controlled by cell genes involved in induction or prevention of programmed cell death (PCD). During embryogenesis PCD implicates cell elimination, necessary in fashioning of the body, moulding of tissues. PCD is often used synonymous with the designation apoptosis, which indicates an endogenous cell suicide program by which useless or crippled cells are eliminated. Apoptosis occurs in normal tissue turnover, in organ involution after withdrawal of trophic hormones, in distinct cells after deprivation of growth factors or specific stimuli and in cells which have undergone sublethal damage. During PCD the nucleus breaks up into DNA fragments of 180-200 kD and the endoplasmic reticulum transforms into vesicles, which are released as apoptotic bodies into the extracellular space. The apoptotic bodies, containing cell organelles and nuclear fragments, are phagocytosed by neighboring cells. Electron micrographs of embryos have revealed the presence of numerous cells with the characteristic features of apoptosis. Experiments, in which small tissue fragments were explanted to other regions, have proven that focal apoptosis is under control of genetic, hormonal and local tissue factors. Morphological analysis has shown that most of the ovarian follicles undergo during development apoptosis, resulting in follicle atresia. Only a small proportion escapes PCD. Growth factors and estrogens have been identified as follicle survival factors, androgens and gonadotropin releasing hormones are potentiating apoptosis of the follicle. An exaggerated PCD or a defective apoptosis during embryogenesis may cause developmental abnormalities. Certain viruses can inhibit apoptosis. while metabolic stress or damage of cell structures can induce apoptosis. Therefore not only viral infections, also drugs and chemical or physical injuries during embryogenesis may interfere with the balanced PCD and thus induce malformations. Drugs and therapy designs directed to modulate the apoptotic process will offer new approaches to the prevention of congenital malformations.
