Profilin1 Regulates Trophoblast Invasion and Macrophage Differentiation

Unexplained recurrent spontaneous abortion (URSA) has been associated with the dysfunction of trophoblasts and decidual macrophages. Current evidence suggests that profilin1 (PFN1) plays an important role in many biological processes. However, little is known about whether PFN1 is related to URSA. Herein, the location of PFN1 was detected by immunohistochemistry, and the level of PFN1 was detected by quantitative real-time PCR, Western blot analysis, and immunohistochemistry. The prolif-eration of trophoblasts was detected by CCK8 and 5-ethynyl-20-deoxyuridine assays, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assays were used to detect apoptosis of trophoblasts. The migration and invasion ability of trophoblasts was assessed by using the wound-healing test and transwell test. Polarization of macrophages was detected in macrophages cultured in trophoblast conditioned medium. PFN1 expression was observed in cytotrophoblasts, syncytiotropho-blasts, and extravillous trophoblasts and was decreased in the villous tissue of patients with URSA. The migration and invasion ability and cell viability of trophoblastic cell lines that underwent PFN1 knockdown significantly decreased, and apoptosis increased. Opposite findings were observed after the overexpression of PFN1 in trophoblastic cells. In addition, PFN1 could regulate trophoblast function through phosphatidylinositol 3-kinase/AKT signal transduction rather than mitogen-activated protein kinase signaling pathways. Finally, knockdown of PFN1 in trophoblasts promoted tumor ne-crosis factor -a secretion to induce macrophage polarization to M1 phenotype, mediated by the NF-kB signaling pathway. These findings indicate that PFN1 has a broad therapeutic potential for patients with URSA.

Automated summary

PFN1 expression was decreased in the villous tissue of patients with URSA. Knockdown of PFN1 in trophoblastic cell lines significantly decreased migration, invasion ability, and cell viability, while increasing apoptosis. Overexpression of PFN1 had the opposite effects. PFN1 regulated trophoblast function through the PI3K/AKT signaling pathway, not the MAPK pathway. Knockdown of PFN1 in trophoblasts promoted tumor necrosis factor-α secretion to induce M1 polarization of macrophages via the NF-kB signaling pathway. These findings suggest that PFN1 has a broad therapeutic potential for patients with URSA.