Phosphatidylinositol-3 kinase/AKT and Fos like protein 1 regulation of trophoblast differentiation

Abstract

Trophoblast cells are one of the earliest lineages to develop in the mammalian embryo. Trophoblast giant cells are the first trophoblast lineage to differentiate and have endocrine and invasive properties. This study focus on the role of the PI3K/AKT signaling pathway in trophoblast giant cell gene expression, steroidogenic potential and invasiveness. Gene profiling of trophoblast populations in the stem, differentiated or differentiated with modified PI3K/AKT signaling states identify genes regulated by PI3K/AKT. These genes are involved in the endocrine and invasive functions of trophoblast and most are upregulated during trophoblast differentiation. Further analysis shows that modification of the PI3K/AKT singling pathway decreases the invasive phenotype of trophoblast and expression of Fos like antigen 1 (FOSL1 or FRA1) a key transcriptional regulator of trophoblast invasion related genes. In summary, we show that FRA1 is a mediator of the PI3K/AKT signaling pathway in regulating gene expression and trophoblast invasion.