Hai-Qiong Liao1,2, Mu-Tian Han1,2, Wei Cheng1,2, Ce Zhang1,2, Hong Li1,2, Ming-Qing Li3, Rui Zhu1,2. 1. Center for Human Reproduction and Genetics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China. 2. State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China. 3. Laboratory for Reproductive Immunology, NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China.
Abstract
PROBLEM: 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. METHOD OF STUDY: 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. RESULTS: 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. CONCLUSION: 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.
PROBLEM: 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. METHOD OF STUDY: 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. RESULTS: 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. CONCLUSION: 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.