Compartmentalized localization of 11β-HSD 1 and 2 at the feto-maternal interface in the first trimester of human pregnancy.

Glucocorticoids are engaged in a number of actions at the feto-maternal interface for the establishment of early pregnancy. However, excessive glucocorticoids can be deleterious to fetal development. Therefore, compartmentalized distribution of 11β-hydroxysteroid dehydrogenase 1 and 2 (11β-HSD1 and 2), which regenerates and inactivates cortisol respectively, would ensure an optimal cortisol concentration at the feto-maternal interface for the establishment of early gestation. However, the distribution pattern of 11β-HSD1 and 2 at the feto-maternal interface in early human pregnancy is not clearly defined. Here we showed that 11β-HSD1 distributed extensively on the maternal side including decidual stromal cells and epithelial cells but scarcely on the fetal side except for localization in the fetal blood vessels of the chorionic villi. In contrast, 11β-HSD2 was abundantly localized in syncytial layer of the chorionic villi and the decidual epithelium. In primary cultures, cortisol upregulated not only 11β-HSD1 expression in decidual stromal cells but also 11β-HSD2 expression in villous trophoblasts of early pregnancy. Further studies revealed that cortisol inhibited the expression of interleukin-1β and 6 in decidual stromal cells and villous trophoblasts, and stimulated expression of human chorionic gonadotropin in villous trophoblasts. Collectively, this study has revealed a compartmentalized distribution pattern of 11β-HSD 1 and 2 at the feto-maternal interface, both of which can be upregulated by glucocorticoids, suggesting that a coordinated interaction between 11β-HSD 1 and 2 may exist to ensure an optimal cortisol concentration at discrete locations at the feto-maternal interface for the establishment of early pregnancy.