Prostaglandin F2α stimulates adhesion, migration, invasion and proliferation of the human trophoblast cell line HTR-8/SVneo. (February 2019)

• Record Type: Journal Article
• Authors: Baryla, Monika; Kaczynski, Piotr; Goryszewska, Ewelina; Riley, Simon C.; Waclawik, Agnieszka
• Is Part Of: Placenta. Volume 77(2019)
• Page Start: 19
• Page End: 29
• Publication Date: 2019-02
• Subjects: Prostaglandin F2α -- Implantation -- HTR-8/SVneo cells -- Trophoblast -- Invasiveness; Placenta -- Periodicals; Reproduction -- Periodicals; Placenta -- Periodicals; Placenta -- Périodiques; Reproduction -- Périodiques; 612.63
• DOI: 10.1016/j.placenta.2019.01.020
• Languages: English
• ISSNs: 0143-4004

Abstract

Abstract: Introduction: The amount of prostaglandin F2α (PGF2α ) in the uterine lumen increases during the window of implantation in many mammals, including humans. We hypothesized that PGF2α regulates processes related to human embryo implantation. Methods: The effect of PGF2α was studied using an 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 PGF2α and fluprostenol were used. PGF2α receptor (PTGFR), MMP9 and MMP2 proteins in the human first trimester placenta were localized by immunohistochemistry and immunofluorescence. 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. PGF2α and fluprostenol increased HTR-8/SVneo cell proliferation and adhesion to extracellular matrix protein (P < 0.05). This effect was abolished by mitogen activated protein kinases (MAPK) inhibitor. PGF2α induced phosphorylation of focal adhesion kinase and MAPK1/3 (P < 0.05). PGF2α increased mRNA content and protein activity of MMP9, and gene and protein expression of interleukin-6 (P < 0.05). EVT cell migration and invasiveness were stimulated by PGF2α (P < 0.05). The PGF2α effect on cell invasion was reduced by inhibitors of MMP2, MMP9 and mTOR. In all experiments, the stimulatory effects of PGF2α were diminished by using a PTGFR antagonist. Discussion: Our findings suggest a significant role for PGF2α in mechanisms associated with implantation. PGF2α 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. Highlights: PGF2α receptor is expressed in human first trimester placenta and in EVT cell line . PGF2α elevates adhesion, proliferation, migration and invasion of human EVT cells . EVT cell proliferation and adhesion are increased by PGF2α-mediated MAPK activation . PGF2α stimulates invasiveness inducing MMP proteolytic activity and mTOR signaling .