Medical Center for Human Reproduction, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People's Republic of China.
Reprod Biol Endocrinol. 2018 Mar 2;16(1):17. doi: 10.1186/s12958-018-0333-2.
Maternal-fetal crosstalk during embryo implantation is complex and regulated by local signaling molecules. Chemokines and their receptors are critical signaling components required for implantation and the process of pregnancy. This study aimed to explore whether human first-trimester trophoblast cells (TCs) were capable of modulating the migration and invasion of human first-trimester decidual epithelial cells (DECs) via CXCL12/CXCR4/CXCR7 signaling.
The expression of CXCR4 and CXCR7 in DECs was examined by immunohistochemistry, immunocytochemistry, immunofluorescence, flow cytometry, real-time polymerase chain reactions and western blotting. The effects of recombinant human CXCL12 (rhCXCL12) and TC-conditioned medium (TC-CM) on DEC viability in vitro were explored using a viability assay. The modulatory effects of rhCXCL12 and TC/DEC co-cultures on DEC migration and invasion were examined with migration/invasion assays.
CXCR4 and CXCR7 were co-expressed in human first-trimester DECs. Human rhCXCL12 and TC-CM had no effects on DEC viability in vitro (P > 0.05). Both exogenous CXCL12 and co-culture with TCs significantly increased the migration and invasion of DECs (P < 0.05). Neutralizing antibodies against CXCR4 (P < 0.05) or CXCL12 (P < 0.05), but not CXCR7 (P > 0.05), significantly blocked the enhanced migration and invasion of DECs induced by exogenous CXCL12 or TC co-culture.
CXCR4 and CXCR7 were co-expressed in human first-trimester DECs. TC-derived CXCL12 promoted the migration and invasion of DECs via CXCR4, but not CXCR7, in a paracrine manner during early pregnancy.
胚胎植入过程中的母子细胞串扰非常复杂，受到局部信号分子的调控。趋化因子及其受体是胚胎植入和妊娠过程所必需的关键信号组成部分。本研究旨在探讨人早孕滋养层细胞（TCs）是否能够通过 CXCL12/CXCR4/CXCR7 信号通路调节人早孕蜕膜上皮细胞（DECs）的迁移和侵袭。
通过免疫组织化学、免疫细胞化学、免疫荧光、流式细胞术、实时聚合酶链反应和 Western blot 检测 DECs 中 CXCR4 和 CXCR7 的表达。采用细胞活力测定法探讨重组人 CXCL12（rhCXCL12）和 TC 条件培养基（TC-CM）对体外 DEC 活力的影响。采用迁移/侵袭测定法检测 rhCXCL12 和 TC/DEC 共培养对 DEC 迁移和侵袭的调节作用。
人早孕 DECs 中共同表达 CXCR4 和 CXCR7。人 rhCXCL12 和 TC-CM 对体外 DEC 活力无影响（P>0.05）。外源性 CXCL12 和与 TCs 共培养均显著增加 DEC 的迁移和侵袭（P<0.05）。抗 CXCR4 中和抗体（P<0.05）或 CXCL12 中和抗体（P<0.05），但不是抗 CXCR7 中和抗体（P>0.05），均可显著阻断外源性 CXCL12 或 TC 共培养诱导的 DEC 迁移和侵袭的增强。
人早孕 DECs 中共同表达 CXCR4 和 CXCR7。TC 衍生的 CXCL12 通过旁分泌方式，通过 CXCR4 而非 CXCR7，在早孕期间促进 DEC 的迁移和侵袭。
