Reproductive Medical Center, Renmin Hospital of Wuhan University & Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, China.
Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.
J Cell Mol Med. 2021 Feb;25(4):2136-2147. doi: 10.1111/jcmm.16191. Epub 2021 Jan 3.
Trophoblasts are important parts of the placenta and exert vital roles in the maternal-foetal crosstalk, and sufficient trophoblasts migration and invasion is critical for embryo implantation and normal pregnancy. Macrophages, as the major components of decidual microenvironment at maternal-foetal interface, can interact with trophoblasts to participate in the regulation of normal pregnancy. Previously, our group have demonstrated that trophoblasts could induce macrophages polarization to M2 subtype by secreting interleukin-6 (IL-6); however, the understanding of macrophages regulating the migration and invasion of trophoblasts is limited. In the present study, we used the co-cultured model to further investigate the effects of macrophages on trophoblasts migration and invasion. Our results showed that co-culture with macrophages promoted epithelial-to-mesenchymal transition (EMT) of trophoblasts, thereby enhancing their migrative and invasive abilities. Further experiments revealed that M2 macrophage-derived G-CSF was a key factor, which promoted the EMT, migration and invasion of trophoblasts via activating PI3K/Akt/Erk1/2 signalling pathway. Clinically, G-CSF was highly expressed in placental villous tissues of normal pregnancy patients compared to patients with recurrent spontaneous abortion, and its expression level was significantly correlation with EMT markers. Taken together, these findings indicate the important role of M2 macrophages in regulating trophoblasts EMT, migration and invasion, contributing to a new insight in concerning the crosstalk between macrophages and trophoblasts in the establishment and maintenance of normal pregnancy.
滋养层是胎盘的重要组成部分，在母胎对话中发挥着重要作用，充足的滋养层迁移和侵袭对于胚胎着床和正常妊娠至关重要。巨噬细胞作为母体-胎儿界面蜕膜微环境的主要组成部分，可以与滋养层相互作用，参与正常妊娠的调节。之前，我们的研究小组已经证明，滋养层可以通过分泌白细胞介素 6（IL-6）诱导巨噬细胞向 M2 亚型极化；然而，对于巨噬细胞调节滋养层迁移和侵袭的理解有限。在本研究中，我们使用共培养模型进一步研究了巨噬细胞对滋养层迁移和侵袭的影响。我们的结果表明，与巨噬细胞共培养促进了滋养层的上皮间质转化（EMT），从而增强了它们的迁移和侵袭能力。进一步的实验表明，M2 巨噬细胞衍生的 G-CSF 是一个关键因素，通过激活 PI3K/Akt/Erk1/2 信号通路促进滋养层的 EMT、迁移和侵袭。临床上，与复发性自然流产患者相比，正常妊娠患者胎盘绒毛组织中 G-CSF 表达水平较高，其表达水平与 EMT 标志物显著相关。总之，这些发现表明 M2 巨噬细胞在调节滋养层 EMT、迁移和侵袭中起着重要作用，为探讨巨噬细胞与滋养层在正常妊娠建立和维持中的相互作用提供了新的认识。
