Institute of Obstetrics and Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.
NHC Key Lab of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Obstetrics and Gynecology Hospital of Fudan University, Fudan University, Shanghai, China.
Am J Reprod Immunol. 2022 Dec;88(6):e13611. doi: 10.1111/aji.13611. Epub 2022 Sep 21.
Placenta accreta (PA) is defined by an abnormal invasion of placental trophoblasts into the myometrium, which can lead to serious postpartum complications. Macrophages play an important role in the regulation of trophoblast function. Both granulocyte colony-stimulating factor (G-CSF) and its receptor (granulocyte colony-stimulating factor receptor, G-CSFR) have effects on trophoblast invasion. However, the current understanding of G-CSF secretion, G-CSFR expression, abnormal polarization of decidual macrophages (dMϕ) in PA and the abnormal invasion of placental trophoblasts into the myometrium are limited.
The polarization of dMϕ in PA was analyzed by flow cytometry (FCM), and the expression of G-CSFR in placental trophoblasts in PA was evaluated by immunohistochemistry. In an in vitro co-culture model, we investigated the effects of HTR-8/SVneo trophoblasts cell line (HTR-8) on macrophage human monocyte cell line (THP-1) polarization and G-CSF secretion, and we also analyzed the effects of THP-1 cells, especially M2-like subtype, on primary trophoblasts and HTR-8 proliferation, invasion, and adhesion. FCM, transwell assays, adhesion assays, and proliferation assays were used in the above model.
Compared with controls (n = 9), dMϕ showed significantly lower levels of M1 markers CD80 and CD86 and higher levels of the M2 markers CD163 and CD206, and G-CSFR expression of placental trophoblasts was increased in PA (n = 5). In vitro experiments showed that the trophoblast HTR-8 cell line induced polarization of THP-1 cells to an M2-like subtype and increased their secretion of G-CSF. Furthermore, IL-4/IL-13-induced M2-like THP-1 macrophages were able to increase the expression of G-CSFR, proliferation, invasion and adhesion of both primary trophoblasts and HTR-8 trophoblasts.
There is an altered immune imbalance at the maternal-fetal interface in PA, which further may lead to abnormal trophoblast function. G-CSF and its receptors may play important roles in abnormal polarization of macrophages and abnormal invasion of trophoblasts.
胎盘部位滋养细胞肿瘤（PA）定义为胎盘滋养细胞异常侵入子宫肌层，可导致严重的产后并发症。巨噬细胞在调节滋养细胞功能方面发挥重要作用。粒细胞集落刺激因子（G-CSF）及其受体（粒细胞集落刺激因子受体，G-CSFR）均对滋养细胞的侵袭有影响。然而，目前对 G-CSF 的分泌、G-CSFR 的表达、PA 中蜕膜巨噬细胞（dMϕ）的异常极化以及胎盘滋养细胞异常侵入子宫肌层的认识有限。
采用流式细胞术（FCM）分析 PA 中 dMϕ 的极化，免疫组织化学法评估 PA 中胎盘滋养细胞的 G-CSFR 表达。在体外共培养模型中，我们研究了 HTR-8/SVneo 滋养细胞系（HTR-8）对巨噬细胞人单核细胞系（THP-1）极化和 G-CSF 分泌的影响，还分析了 THP-1 细胞，特别是 M2 样亚型，对原代滋养细胞和 HTR-8 增殖、侵袭和黏附的影响。在上述模型中，采用流式细胞术、Transwell 实验、黏附实验和增殖实验。
与对照组（n=9）相比，PA 中 dMϕ 的 M1 标志物 CD80 和 CD86 水平显著降低，M2 标志物 CD163 和 CD206 水平显著升高，胎盘滋养细胞的 G-CSFR 表达增加（n=5）。体外实验表明，滋养细胞系 HTR-8 诱导 THP-1 细胞向 M2 样表型极化，并增加其 G-CSF 的分泌。此外，IL-4/IL-13 诱导的 M2 样 THP-1 巨噬细胞能够增加原代滋养细胞和 HTR-8 滋养细胞的 G-CSFR 表达、增殖、侵袭和黏附。
PA 中母体-胎儿界面存在免疫失衡改变，可能进一步导致滋养细胞功能异常。G-CSF 和其受体可能在巨噬细胞的异常极化和滋养细胞的异常侵袭中发挥重要作用。
