Placental 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2), a glucocorticoid-catalyzing enzyme, prevents active glucocorticoids from maternal circulation into the fetus, thus protecting against IUGR.
It is known that inhibiting 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) expression in the placenta can cause fetal over-exposure to maternal glucocorticoids and induce intrauterine growth restriction (IUGR); these effects ultimately increase the risk of adult chronic diseases.
Impaired placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) activity which inactivates maternal glucocorticoids is associated with poor fetal growth and a higher risk of chronic diseases in adulthood.
In addition, significantly elevated odds of FGR birth were associated with increasing DNA methylation of HSD11B2 and WNT2, and decreasing DNA methylation of IGF2.
11beta-HSD1 protein levels were reduced in amnion and 11beta-HSD1 and 11beta-HSD2 oxidase activity in decidua and cotyledon were reduced from pregnancies with IUGR.
Taken together, our present findings provide evidence suggesting a role for an attenuated placental as well as fetal 11beta-HSD2 in the pathogenesis of IUGR.
This suggests that the reduced placental 11beta-HSD2 in FGR is not due to intrinsic abnormalities in trophoblast cells, but likely a result of extrinsic factors associated with FGR.
No mutations were found in the 11beta-HSD2 gene in the intrauterine growth restriction cohort, and imprinting analysis revealed that the 11beta-HSD2 gene was not imprinted.