Abstract
BackgroundMaternal-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.MethodThe 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.ResultCXCR4 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.ConclusionsCXCR4 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.
Highlights
Maternal-fetal crosstalk during embryo implantation is complex and regulated by local signaling molecules
Steroid hormones showed priming effects on C-X-C chemokine receptor type 4 (CXCR4) and C-X-C chemokine receptor type 7 (CXCR7) expression in human cycling and early pregnant Decidual stroma cells (DSC) before the emergence of an embryo [14, 15]. These results indicate the potential importance of the C-X-C motif chemokine ligand 12 (CXCL12)/CXCR4/CXCR7 axis in implantation and early pregnancy
The in vitro viability of Decidual epithelial cell (DEC) was not affected by treatment with CXCL12 or Trophoblast cell (TC)-CM, supporting previous findings from our team showing that the CXCL12/CXCR4 axis had no effect on the viability or PCNA expression of DSCs in vitro [12, 13]
Summary
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. The application of assisted reproductive technology (ART) in the clinic has made great achievements in infertility treatment. Successful implantation requires the perfect coordination between the fetal-derived trophoblasts (TCs) and maternal-derived decidual cells via a complex network of molecules signaling in an autocrine and paracrine manner. Zheng et al Reproductive Biology and Endocrinology (2018) 16:17 factors and cytokines [3,4,5,6,7,8]. Deficient glandular activity has been observed in some recurrent miscarriages, further implying an important role for endometrial glands in pregnancy [6]
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