It is known that basal glucocorticoid levels in utero are essential for regulating fetal development and maturation, and determine the fate of later life. Recently, more and more studies suggest that adverse prenatal environments may cause abnormal maternal glucocorticoid levels in utero. 11β-hydroxysteroid dehydrogenases (11β-HSDs) are widely distributed in the target organs of glucocorticoids (GCs) and mineralocorticoids. 11β-HSDs is involved in fetal physiological and pathological development by activating or inactivating GCs. Prenatal adverse environments (including exogenous and maternal environments) can affect the expression and activity of 11β-HSDs in the placenta and fetus via multiple pathways. It induces abnormal local glucocorticoid levels in fetal multiple tissues, fetal developmental programming and homeostasis changes, and the susceptibility to various diseases after birth. We also discuss the interventions of 11β-HSDs inhibitors on fetal developmental programming and susceptibility to multiple diseases. Finally, we propose that 11β-HSD2 can be used as a molecular target for fetal developmental toxicity, while 11β-HSD1 can be regarded as an intervention target to prevent fetal-originated diseases. This review will provide a theoretical basis for the early prevention and treatment of fetal-originated diseases.
Keywords: 11β-hydroxysteroid dehydrogenase system; Adult diseases susceptibility; Fetal development; Glucocorticoid; Prenatal adverse environments.
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