Hypoxia-induced polarization of M2 macrophages and CCL5 secretion promotes the migration and invasion of trophoblasts

Biol Reprod. 2022 May 19:ioac100. doi: 10.1093/biolre/ioac100. Online ahead of print.ABSTRACTIn the early stage of pregnancy, hypoxia in the placenta is of great significance to the migration and invasion of trophoblasts. In addition, changes to the polarity and activity of macrophages can affect embryo implantation, trophoblast migration and invasion, and vascular remodeling by affecting cytokine secretion. However, the mechanism of the effects of hypoxic conditions in the placenta on trophoblasts remains unknown. We used gene knockdown on macrophages, and drug treatment on trophoblasts, and cultured them under hypoxic and normoxic conditions. The cells were then subjected to wound healing assays, Transwell cell invasion experiments, quantitative real-time reverse transcription PCR, western blotting, and immunofluorescence. The polarization of macrophages in each group, the migration and invasion ability of trophoblasts, and changes to the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway were detected. Hypoxic conditions induce M2 polarization of macrophages. The conditioned medium from macrophages under hypoxic conditions increased the migration and invasion of trophoblasts, and enhanced the levels of phosphorylated (p)-PI3K and p-AKT in trophoblasts. After CCL5 knockdown in macrophages, the ability of conditioned medium from macrophages cultured under hypoxic conditions to promote the migration and invasion of trophoblasts was ...
Source: Biology of Reproduction - Category: Reproduction Medicine Authors: Source Type: research