Abstract
Embryo implantation is a complex process regulated by a network of biological molecules. Recently, it has been described that fractalkine (CX3CL1, FKN) might have an important role in the feto–maternal interaction during gestation since the trophoblast cells express fractalkine receptor (CX3CR1) and the endometrium cells secrete fractalkine. CX3CR1 controls three major signalling pathways, PLC-PKC pathway, PI3K/AKT/NFκB pathway and Ras-mitogen-activated protein kinases (MAPK) pathways regulating proliferation, growth, migration and apoptosis. In this study, we focused on the molecular mechanisms of FKN treatment influencing the expression of implantation-related genes in trophoblast cells (JEG-3) both in mono-and in co-culture models. Our results reveal that FKN acted in a concentration and time dependent manner on JEG-3 cells. FKN seemed to operate as a positive regulator of implantation via changing the action of progesterone receptor (PR), activin receptor and bone morphogenetic protein receptor (BMPR). FKN modified also the expression of matrix metalloproteinase 2 and 9 controlling invasion. The presence of HEC-1A endometrial cells in the co-culture contributed to the effect of fractalkine on JEG-3 cells regulating implantation. The results suggest that FKN may contribute to the successful attachment and implantation of embryo.
Highlights
Embryo implantation, the process of attachment and invasion of the uterus endometrium by the conceptus, is a complex physiological process tightly regulated by multiple biological molecules
Our results suggest that HEC-1A cells contribute to the implantation by altering the expression of implantation-related genes and proteins, which could contribute to the action of fractalkine in trophoblast cells
Recent publications revealed that FKN might regulate adhesion and migration of trophoblast cells at different stages of pregnancy [14,55] and the FKN-CX3CR1 axis was suggested to be implicated in the maternal-fetal communication [13]
Summary
The process of attachment and invasion of the uterus endometrium by the conceptus, is a complex physiological process tightly regulated by multiple biological molecules. Implantation requires a well orchestrated interaction between maternal and foetal tissues and consists of a fine balanced cross talk of cytokines, hormones and chemokines [1,2]. The chemokine fractalkine (FKN) is synthesized as a 373 amino-acid transmembrane molecule. It is the only CX3C-chemokine which has been described [4,5]. Its function is not merely chemoattraction, but it acts as an adhesion molecule and is capable of regulating the immune response via CX3CR1 corresponding receptor interaction [5,6,7]
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