Prostaglandin F2α stimulates adhesion, migration, invasion and proliferation of the human trophoblast cell line HTR-8/SVneo

Abstract Introduction The amount of prostaglandin F 2α (PGF 2α ) in uterine lumen increases during the window of implantation in many mammals, including humans. We hypothesized that PGF 2α regulates processes related to human embryo implantation. Methods Effect of PGF 2α was studied using in vitro model of human extravillous trophoblast (EVT) cell line (HTR-8/SVneo). Adhesion, proliferation, invasion and migration assays, zymography for metalloproteinases (MMP) activity, and gene/protein expression analyses were applied. Doses of 100 nM and/or 1 μM of PGF 2α and fluprostenol were used. PGF 2α receptor (PTGFR), MMP9 and MMP2 proteins in the human first trimester placenta were localized by immunohistochemistry and immunofluoroscence. Results This study is the first reporting the expression of PTGFR protein in the first trimester placenta, as well as in HTR-8/SVneo cells. PGF 2α and fluprostenol increased HTR-8/SVneo cell proliferation and adhesion to extracellular matrix protein (P  2α induced phosphorylation of focal adhesion kinase and MAPK1/3 (P  2α increased mRNA content and protein activity of MMP9, and gene and protein expression of interleukin-6 (P  2α (P  2α effect on cell invasion was reduced by inhibitors of MMP2, MMP9 and mTOR. In all experiments, the stimulatory effects of PGF 2α were diminished by using a PTGFR antagonist. Discussion Our findings suggest a significant role for PGF 2α in mechanisms associated with implantation. PGF 2α acting by PTGFR in HTR-8/SVneo cells stimulates their adhesion and proliferation through the MAPK signaling pathway and increases invasiveness inducing MMP proteolytic activity and mTOR signaling.