ould act acutely to affect differentiated trophoblast cell function. Several of the differentiation associated genes KPT-185 were also sensitive to acute disruption of the PI3K signaling pathway. PI3K regulation of trophoblast steroidogenesis Trophoblast giant cells are known sites for the biosynth esis Inhibitors,Modulators,Libraries of progesterone and androstenedione. Sev eral genes encoding proteins involved in the biosynthesis of steroid hormones are upregulated during trophoblast differentiation. These include Star, which encodes a protein involved in transporting cholesterol to the mitochondria, and a series of genes encoding enzymes responsible for the production of progesterone and androstenedione. Hsd3b1 and Cyp17a1 expression were positively regulated by PI3K signaling.

Consistent with this observation, the production of androstenedione by dif ferentiating trophoblast cells was also dependent upon PI3K. Discussion Organization of the hemochorial placenta is the result Inhibitors,Modulators,Libraries of signaling pathways directing the expansion and differen tiation of trophoblast stem cell and progenitor cell populations. This decision making culminates in the sys tematic activation and inactivation of gene networks within trophoblast cell populations and elaboration of specific functions that facilitate redirection of resources from the mother to the fetus. In this report, we utilized the Rcho 1 trophoblast stem cell model and induced dif ferentiation through increased cell density and removal of growth stimuli. The growth factor deprivation may also lead to activation of stress pathways, which have been shown to influence trophoblast differentiation.

Using this strategy, we have identified genes associated with trophoblast stem cell expansion, differentiation, and those impacted by the PI3K signaling pathway. Trophoblast stem cell associated genes Stem cells Inhibitors,Modulators,Libraries possess the potential to proliferate and to dif ferentiate. Several genes implicated in maintenance of the trophoblast stem cell state were identified in Rcho 1 trophoblast stem cells and are similarly present in mouse trophoblast stem cells. These include an assort ment of genes implicated as cell cycle regulators in numerous cell types and also genes that have been more specifically shown to have a role in the specification and maintenance of trophoblast stem cells. Phlda2 displayed one of the most striking differences in its expression profile in stem versus differentiated cells.

It was high in stem cells and virtually undetectable follow ing differentiation, which is also found in mouse tropho blast stem cells. Phlda2 is intriguing for a number Inhibitors,Modulators,Libraries of reasons. Phlda2 is an imprinted gene GSK-3 exhibiting maternal allele specific expression in extraembryonic and embryo nic structures and in postnatal tissues, including the kid ney. In the mouse, disruption of the Phlda2 gene leads to placental overgrowth, while overexpression of Phlda2 results in placental growth restriction. Given that PHLDA2 restrains Z-VAD-FMK msds placental growth it seems counter intuitive that it wo