Center for Human Reproduction and Genetics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China.
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
Am J Reprod Immunol. 2021 Aug;86(2):e13406. doi: 10.1111/aji.13406. Epub 2021 Mar 24.
During the first trimester, the accumulation of macrophages, which is the second largest decidual leukocyte population (~20%) at the maternal-fetal interface, is quite vital for a successful pregnancy, including embryo implantation, trophoblast invasion, and vascular remodeling. The mechanism of the enrichment and redistribution of macrophages in the uterine decidua of early pregnancy is largely unclear.
A total of 37 women with normal early pregnancies were included. Primary decidual macrophages (dMφs) (n = 37) and primary decidual stromal cells (DSCs) (n = 37) were isolated, and the adhesion molecules were analyzed by flow cytometry (FCM). Adhesive experiment was carried out to evaluate the adhesion capacity by counting cell numbers of dMφs adhered to DSCs in a co-culture system.
We found that RANK dMφs was the dominating subtype at the maternal-fetal interface. The expression of adhesion molecules (eg, CD29, CD31, CD54, and CD62L) on the surface of RANK dMφs was higher than that of RANK dMφs. After co-culture with DSCs, the expression of adhesion molecules on dMφs was up-regulated in a RANKL-dependent manner. Meanwhile, dMφs promoted the releasing of RANKL on DSCs after co-culture. Consistently, dMφs exhibited the lessoned capacity of adhesion to DSCs when blocking the crosstalk of RANKL-RANK between the DSCs and dMφs in vitro.
These results suggest that the interaction of RANKL-RANK up-regulates the expression of adhesion molecules on the surface of dMφs, contributing to the accumulation and residence of dMφs in human early pregnancy.
在妊娠早期，巨噬细胞的积累对于成功妊娠至关重要，它是母胎界面上第二大蜕膜白细胞群体（~20%），包括胚胎着床、滋养层浸润和血管重塑。巨噬细胞在妊娠早期子宫蜕膜中的富集和再分布的机制在很大程度上尚不清楚。
共纳入 37 例正常早孕妇女。分离原代蜕膜巨噬细胞（dMφs）（n=37）和原代蜕膜基质细胞（DSCs）（n=37），并用流式细胞术（FCM）分析黏附分子。通过计数共培养体系中 dMφs 黏附到 DSCs 的细胞数，进行黏附实验来评估黏附能力。
我们发现母胎界面上以 RANK dMφs 为主导亚型。RANK dMφs 表面黏附分子（如 CD29、CD31、CD54 和 CD62L）的表达高于 RANK dMφs。与 DSCs 共培养后，dMφs 表面黏附分子的表达呈 RANKL 依赖性上调。同时，共培养后 dMφs 促进了 DSCs 释放 RANKL。一致的是，当体外阻断 DSCs 和 dMφs 之间的 RANKL-RANK 串扰时，dMφs 黏附到 DSCs 的能力降低。
这些结果表明，RANKL-RANK 的相互作用上调了 dMφs 表面黏附分子的表达，有助于 dMφs 在人早孕中的积累和驻留。
