Changes in the placental glucocorticoid barrier during rat pregnancy: impact on placental corticosterone levels and regulation by progesterone.

Glucocorticoid excess in utero inhibits fetal growth and programs adverse outcomes in adult offspring. Access of maternal glucocorticoid to the glucocorticoid receptor (NR3C1) in the placenta and fetus is regulated by metabolism via the 11beta-hydroxysteroid dehydrogenase (HSD11B) enzymes, as well as multidrug resistance P-glycoprotein (ABCB1)-mediated efflux of glucocorticoids from the syncytiotrophoblast. This study determined expression of genes encoding the two HSD11B isoforms (Hsd11b1 and Hsd11b2), the two ABCB1 isoforms (Abcb1a and Abcb1b), and Nr3c1 in the junctional and labyrinth zones of rat placentas at Days 16 and 22 of normal gestation (Day 23 is term).

Glucocorticoids prevent the normal increase in placental vascular endothelial growth factor expression and placental vascularity during late pregnancy in the rat.

Increased glucocorticoid exposure reduces fetal growth and predisposes to an increased risk of disease in later life. In addition to direct effects on fetal growth, glucocorticoids also compromise fetal growth indirectly via detrimental effects on placental growth and function. The current study investigated the effects of dexamethasone-induced intrauterine growth restriction on placental vascular development and expression of the endothelial cell-specific mitogen, vascular endothelial growth factor (VEGF).

Placental expression of secreted frizzled related protein-4 in the rat and the impact of glucocorticoid-induced fetal and placental growth restriction.

Wnt genes regulate a diverse range of developmental processes, including placental formation. Activation of the WNT pathway results in translocation of beta-catenin (CTNNB1) into the nucleus and the subsequent activation of transcription factors that promote proliferation. The secreted frizzled related proteins (SFRPs) are thought to inhibit WNT signaling by binding to the WNT ligand or its frizzled receptor.

Placental expression of peroxisome proliferator-activated receptors in rat pregnancy and the effect of increased glucocorticoid exposure.

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors. Recent gene deletion studies indicate that PPARG and PPARD play critical roles in rodent development, including effects on placental vascularization. In this study we investigated the expression of the PPAR isoforms and their heterodimeric partner, RXRA, in the two functionally and morphologically distinct zones of the rat placenta during normal gestation and after glucocorticoid-induced fetal and placental growth restriction.