Steroid Receptor Coactivator-2 Controls Human Extravillous Trophoblast Cell Proliferation, Migration, and Invasion

Abnormal placentation is a fundamental cause of pregnancy complications including preeclampsia, miscarriage, and intrauterine growth restriction. Proliferation, differentiation, migration, and invasion are key properties of trophoblast cells that regulate trophoblast functions. Imbalance of these cellular processes is linked to placental pathologies. Using HTR-8/SVneo immortalized human trophoblast cells, we demonstrate that steroid receptor coactivator-2 (SRC-2), a transcriptional regulator of nuclear receptors, is essential for extravillous trophoblast cell proliferation, migration, and invasion. Genome-wide transcriptomics identified an SRC-2–dependent transcriptome in HTR-8/SVneo cells that includes a diverse spectrum of proteins involved in placental tissue development and function. To emphasize the utility of this transcriptomics data set, we demonstrate that WNT family member 9A (WNT9A) is not only a molecular target of SRC-2 but also crucial for maintaining many of the cellular properties of human extravillous trophoblast cells. Overall design: To investigate the SRC-2 gene signature in regulating human extravillous trophoblast cells, HTR8/Svneo cells were used. Total RNA was isolated from NT siRNA and SRC-2 siRNA-treated HTR8 cells and subjected to the RNAseq assay.