NHC Key Lab of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China.
Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacy, Fudan University, Shanghai, China.
Reproduction. 2022 Mar 10;163(5):241-250. doi: 10.1530/REP-21-0282.
Decidual stromal cells (DSCs) modulate the function of trophoblasts through various factors. Wnt signaling pathway is active at the maternal-fetal interface. Here, we isolated endometrial stromal cells (ESCs) from women of reproductive ages and DSCs from normal pregnancy during the first trimester (6-10 weeks). Real-time quantitative PCR and western blotting were used to screen out the most variable WNT ligands between ESCs and DSCs, which turned out to be WNT16. Both culture mediums from DSCs and recombinant protein of human WNT16 enhanced the survival and invasion of HTR8/SVneo trophoblastic cells. Furthermore, the regulation of DSCs on trophoblast was partly blockaded after we knocked down WNT16 in DSCs. Treating HTR8/SVneo trophoblastic cells with small molecular inhibitors and small interfering RNA (siRNA), we found that the activity of AKT/beta-catenin (CTNNB1) correlated with the effect of WNT16. The crosstalk of WNT16/AKT/beta-catenin between DSCs and trophoblasts was determined to be downregulated in unexplained recurrent spontaneous abortion. This study suggests that WNT16 from DSCs promotes HTR8/SVneo trophoblastic cells invasion and survival via AKT/beta-catenin pathway at the maternal-fetal interface in human early pregnancy. The disturbance of this crosstalk between DSCs and trophoblasts might cause pregnancy failure.
蜕膜基质细胞（DSC）通过各种因子调节滋养细胞的功能。Wnt 信号通路在母胎界面处活跃。在此，我们从生殖年龄段的女性中分离出子宫内膜基质细胞（ESC），并从正常妊娠的早期（6-10 周）中分离出 DSC。实时定量 PCR 和 Western blot 用于筛选 ESC 和 DSC 之间最具差异的 WNT 配体，结果发现是 WNT16。DSC 的培养基和人源 WNT16 的重组蛋白均增强了 HTR8/SVneo 滋养细胞的存活和侵袭能力。此外，在 DSC 中敲低 WNT16 后，DSC 对滋养细胞的调节部分被阻断。用小分子抑制剂和小干扰 RNA（siRNA）处理 HTR8/SVneo 滋养细胞，我们发现 AKT/β-连环蛋白（CTNNB1）的活性与 WNT16 的作用相关。在不明原因的复发性自然流产中，DSC 和滋养细胞之间的 WNT16/AKT/β-连环蛋白相互作用被确定下调。本研究表明，DSC 中的 WNT16 通过 AKT/β-连环蛋白途径促进 HTR8/SVneo 滋养细胞的侵袭和存活，这在人类早孕的母胎界面中起作用。DSC 和滋养细胞之间这种相互作用的紊乱可能导致妊娠失败。
