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 currently known on whether PFN1 is related to URSA. The location of PFN1 was detected by immunohistochemistry. The level of PFN1 were detected by qRT-PCR, western blot and immunohistochemistry. The proliferation of trophoblasts was detected by CCK8 and EdU assays. Apoptosis of trophoblasts was detected by TUNEL assays. The migration and invasion ability of trophoblasts were assessed by the wound-healing test and transwell test. Macrophages were cultured in trophoblast conditioned medium and the polarization of macrophages was detected. PFN1 expression was observed in in cytotrophoblasts, syncytiotrophoblasts, and extravillous trophoblasts and decreased in the villous tissue of URSA patients. 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 following the overexpression of PFN1 in trophoblastic cells. In addition, PFN1 could regulate trophoblast function through PI3K/AKT signal transduction rather than MAPK signaling pathways. In addition, this study also found that knockdown of PFN1 in trophoblast promotes TNF-α secretion to induce macrophage polarization to M1 phenotype, mediated by the NF- κ B signaling pathway.