LIF upregulates poFUT1 expression and promotes trophoblast cell migration and invasion at the fetal-maternal interface.

Abstract

Trophoblast cell migration and invasion are crucial for the establishment of a successful pregnancy. Protein O-fucosyltransferases, such as poFUT1 and poFUT2, catalyze the O-fucosylation of proteins and have important roles in embryonic development. Leukemia inhibitory factor (LIF) is a critical cytokine in the regulation of embryonic development and implantation. However, the exact roles of poFUTs in embryo migration and invasion and the effects of LIF on the expression of poFUTs have not been studied in detail. In the current study, we showed that poFUT1 and LIF were highly expressed in human trophoblast cells and in the serum of women during the first trimester of a normal pregnancy. However, in patients with threatened abortion, poFUT1 and LIF levels were found to be reduced. There were no significant differences in the expression levels of poFUT2 between the two groups. The migration and invasion potential of trophoblasts in an explant culture and in an in vitro implantation model was decreased or increased upon altering poFUT1 expression levels by siRNA or cDNA transfection. Our results also revealed that LIF upregulated the expression of poFUT1. The upregulation of poFUT1 by LIF promoted trophoblast cell migration and invasion at the fetal–maternal interface by activating the PI3K/Akt signaling pathway. Taken together, these study findings suggest that poFUT1 may be used as a marker of embryo implantation.