Fetal protection from maternal cortisol: How early is 11-beta hydroxysteroid dehydrogenase type 2 (11β-HSD2) expressed in the human placenta

摘要

Maternal physiologic stress during gestation has been associated with negative developmental outcomes, including intra-uterine growth restriction and reduced birth weight, which can impact postnatal development, behaviour and health. The human fetus is partially protected from elevated cortisol exposure by placental 11-beta hydroxysteroid dehydrogenase type 2 (11β-HSD2), an enzyme which oxidizes bioactive cortisol into bio-inactive cortisone. In humans, placental 11β-HSD2 has been shown to be present from as early as the middle of the first trimester until parturition. However, the onset of placental 11β-HSD2 expression has yet to be clearly established. Given the protective role this enzyme is hypothesized to have during gestation, we predicted that placental 11β-HSD2 expression should begin during the earliest stages of the placentation process, the critical peri-conceptional period. Specifically, we predicted that this enzyme's expression should be most conspicuous in cells that are in intimate contact with the mother's circulatory system. We performed immunocytochemical analysis of placentas collected 3 to 6 weeks post-conception. Consistent with our predictions, 11β-HSD2 was present as early as 3 weeks post-conception in syncytiotrophoblasts, where most maternal-fetal exchange occurs, and in columnar epithelial cells encircling uterine endometrial glands, which provide early histiopathic nutrition to the embryo. 11β-HSD2 expression in these critical maternal-fetal exchange areas is consistent with its hypothesized role as a protective barrier to modulate embryonic/fetal exposure to cortisol of maternal origin. Further research is necessary to investigate which mechanisms, if any, protect the conceptus before the onset of placentation.