Glucocorticoid signaling regulates cell invasion and migration in the human first-trimester trophoblast cell line Sw.71.

Abstract

The development of the placenta and its functions are sensitive to infection and stress, which can activate the hypothalamic-pituitary-adrenal axis. Adrenally produced glucocorticoids are the body's primary mediators of the inflammatory and stress response. Although the glucocorticoid receptor (GR) is expressed in all human villous trophoblast tissue, the effect of glucocorticoids on placentation is not well understood. Using microarray analysis, we identified the glucocorticoid-regulated transcriptional profile in the immortalized first-trimester extravillous trophoblast cell line Swan.71 (Sw.71). The synthetic glucocorticoid dexamethasone significantly regulated 3829 genes, including genes associated with cell movement, growth, and survival. SERPINE1, an inhibitor of trophoblast invasion, was induced by glucocorticoids in Sw.71 cells and is associated with the pathogenesis of preeclampsia. Glucocorticoid treatment induced recruitment of activated polymerase II and GR to the SERPINE1 promoter, suggesting a mechanism for transcriptional regulation. Functionally, glucocorticoid treatment inhibited cell proliferation, migration, and invasion. These findings suggest that glucocorticoids regulate extravillous trophoblast functions by altering the gene expression profile, which may contribute to the pathogenesis of reproductive disorders such as preeclampsia and IUGR.