Glucocorticoid Programming Mechanism of Fetal-Originated Diseases

Glucocorticoids play a critical role in regulating fetal development and maturation as well as determining the fate of the fetus after birth. The author’s previous studies have demonstrated that adverse environments during pregnancy can compromise the placental glucocorticoid (GC) barrier, resulting in excessive maternal GC exposure in fetuses and inducing intrauterine growth retardation (IUGR). This can lead to developmental programming of multiple organs, changes in homeostasis, and susceptibility to related diseases through abnormal epigenetic modification. The team has further proposed that intrauterine maternal GC exposure is an “active compensatory” response of the mother to promote fetal survival in an adverse environment during pregnancy, inducing the development of a “thrifty phenotype.” The team has innovatively proposed that “two-programming and two-strike” occurs in fetal-originated diseases caused by adverse environments during pregnancy. Among these, the “GC-insulin-like growth factor 1 axis” mediates IUGR, catch-up growth after birth, and susceptibility to multiple diseases in adulthood.