Pregnancy

Spatial and Temporal Patterns of Expression of 11ß-Hydroxysteroid Dehydrogenase Types 1 and 2 Messenger RNA and Glucocorticoid Receptor Protein in the Murine Placenta and Uterus During Late Pregnancy

Abstract

To gain insight into the role of 11ß-hydroxysteroid dehydrogenase (11ß-HSD) enzymes and actions of glucocorticoids in the murine placenta and uterus, the expression pattern of the mRNA for 11ß-HSD1 and 2, and the glucocorticoid receptor (GR) protein, was determined from embryonic day 12.5 (E12.5, term=E19) to E18.5 by in situ hybridization and immunohistochemistry, respectively. Consistent with its putative role in regulating the trans-placental passage of maternal glucocorticoid to the fetus, 11ß-HSD2 mRNA was highly expressed in the labyrinthine zone (the major site of maternal/fetal exchange) at E12.5, and its level decreased dramatically at E16.5, when it became barely detectable. Remarkably, the silencing of 11ß-HSD2 gene expression coincided with the onset of 11ß-HSD1 gene expression in the labyrinth at E16.5 when moderate levels of 11ß-HSD1 mRNA were detected and maintained to E18.5. By contrast, neither 11ß-HSD1 mRNA nor 11ß-HSD2 mRNA was detected in any cell types within the basal zone from E12.5 to E18.5. Moreover, the expression of 11ß-HSD1 and 2 in the decidua exhibited a high degree of cell specificity in that the mRNA for both 11ß-HSD1 and 2 was detected in the decidua-stroma, but not in the compact decidua. A distinct pattern was also observed within the endometrium where the mRNA for 11ß-HSD1 was expressed in the epithelium while that for 11ß-HSD2 was confined strictly to the stroma. By comparison, the expression of GR in the placenta and uterus was ubiquitous and unremarkable throughout late pregnancy. In conclusion, the present study demonstrates, for the first time, remarkable spatial and temporal patterns of expression of 11ß-HSD1 and 2 and GR in the murine placenta and uterus, and highlights the intricate control of not only trans-placental passage of maternal glucocorticoid to the fetus but also local glucocorticoid action during late pregnancy.