Developmental Toxicity of Dexamethasone and Related Fetal-Originated Disease

Dexamethasone, a synthetic glucocorticoid, is widely used to treat preterm labor and related diseases during pregnancy. However, the prenatal application of dexamethasone has a “double-edged sword” effect. Based on the latest research, this chapter summarizes the fetal developmental toxicity of dexamethasone, its long-term susceptibility to disease, and proposes a systematic intrauterine programming mechanism of fetal developmental toxicity and susceptibility to adult disease induced by dexamethasone. The mechanism of developmental toxicity is related to its direct effect on dexamethasone and the indirect effect of endogenous glucocorticoid reduction in vivo, both of which cause abnormal epigenetic modification (i.e., two-programming mechanisms). Intrauterine dexamethasone exposure can also lead to the multigenerational inheritance of altered programming in offspring’s multiple organs by changing the epigenetic reprogramming in germ cells. This chapter contributes to a comprehensive understanding of the developmental toxicity of dexamethasone and provides a theoretical and experimental basis for guiding the rational application of dexamethasone during pregnancy and early prevention and treatment of related fetal-originated diseases.