Mechanisms of the embryo's response to embryopathic stressors: a focus on p53.
Whether the embryo develops normally or not depends not only on the mechanisms regulating embryonic development, but also on the mechanisms acting to resist and repair injures in the embryo due to harmful maternal stimuli or exposure to developmental toxicants. The key role of p53 in the regulation of the embryo's response to embryopathic stress inducing DNA damage is beyond doubt. Yet, the question why p53 in some cases acts as a suppressor of teratogenesis, whereas in other cases it induces teratogenesis, remains unanswered. In this minireview we analyze studies in which organogenesis-stage embryos were exposed to various developmental toxicants and suggest a model unifying the teratogenesis-suppressing and teratogenesis-promoting role of p53. This model predicts that p53 protects embryos from developmental toxicant inducing oxidative stress and promotes the process of maldevelopment induced by developmental toxicants activating apoptotic machinery. Certainly, many questions must be answered before concluding the extent to which this model is correct. Yet, it does allow us to explain some discrepancies obtained in studies performed to date. Also, the model might be useful in choosing molecular targets for further studies addressing p53-controlled and p53-independent mechanisms, which determine the embryo's resistance to embryopathic stress.
Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv, 69978, Israel. arkadyt@post.tau.ac.il
Arkady
A
Torchinsky
Vladimir
V
Toder
D000818:Animals; D004622:Embryo, Mammalian / Q000276:immunology* / Q000378:metabolism; D047108:Embryonic Development / Q000276:immunology*; D005260:Female; D006801:Humans; D018448:Models, Immunological; D018384:Oxidative Stress / Q000276:immunology; D011247:Pregnancy; D013312:Stress, Physiological / Q000276:immunology*; D013723:Teratogens / Q000633:toxicity; D016159:Tumor Suppressor Protein p53 / Q000276:immunology* / Q000378:metabolism
D013723:Teratogens; D016159:Tumor Suppressor Protein p53