[Transplacental teratogenesis]

Exposure during pregnancy to drugs or environmental chemicals (named xenobiotics) may cause birth defects in the embryo. Little is known about the biochemical and molecular mechanisms of teratological susceptibility. Many embryotoxic xenobiotics are proteratogens when bioactivated by enzymes, such as cytochromes, peroxidases and prostaglandin synthase to reactive intermediary metabolites. These intermediates are free radicals or electrophiles, that oxidize or bind irreversibly to cellular macromolecules such as DNA, proteins and lipids, altering cellular function. Teratological susceptibility is determined by a balance among maternal xenobiotic elimination, embryonic bioactivation and detoxification of reactive intermediates, cytoprotection and repair of molecular lesions. The embryo is relatively susceptible to reactive intermediates due to immature pathways for the detoxification, cytoprotection and repair. In this way, teratogenesis can occur from exposure to therapeutic concentrations of drugs or low concentrations of environmental chemicals.