274. Placental expression of secreted frizzled related protein (sFRP4) in the rat: association with β-catenin localization and regulation by glucocorticoids

Abstract

Wnt genes regulate a diverse range of developmental processes including placental development. Activation of the wnt pathway results in nuclear translocation of β-catenin and activation of the TCF/Lef family of transcription factors. The secreted frizzled related proteins (sFRPs) modulate wnt signaling by binding to either the wnt ligand or its transmembrane frizzled receptor. The current study examined the spatial and temporal expression of one of these secreted molecules, sFRP4, in the rat placenta over the final third of pregnancy, and whether associated changes occurred in the expression and localization of β-catenin. The expression of sFRP4 and β-catenin was also analysed in a model of glucocorticoid-induced placental growth restriction. Analysis by quantitative RT-PCR over the final third of pregnancy demonstrated a dramatic increase in sFRP4 mRNA (14-fold, P < 0.001) specifically within the basal zone of the placenta near term. In situ hybridization and immunohistochemistry localized sFRP4 expression primarily to giant trophoblasts of the basal zone. In addition, sFRP4 protein was notably upregulated in association with a restricted nuclear translocation of β-catenin. Maternal dexamethasone treatment (1 μg/mL in drinking water; day 13–22) further increased the expression of sFRP4 mRNA in both the basal (120%, P < 0.05) and labyrinth (285%, P < 0.01) zones of the placenta at day 22 (term = 23 days) compared to untreated controls. These data indicate that sFRP4 expression is increased in the basal zone of the rat placenta, the major site of apoptosis in late pregnancy, and is further stimulated by glucocorticoids. Moreover, the observed inhibition of β-catenin expression and its nuclear translocation suggest that sFRP4 inhibition of wnt signaling in the placenta may contribute to placental apoptosis and ultimately fetal growth restriction.