Profiles of cytokines secreted by isolated human endometrial cells under the influence of chorionic gonadotropin during the window of embryo implantation

Kallol K Roy,Akhilesh Srivastava,Debabrata Ghosh,Jayasree Sengupta,Alka Kriplani

doi:10.1186/1477-7827-11-116

Kallol K Roy, Akhilesh Srivastava + Show 3 more

Open Access

https://doi.org/10.1186/1477-7827-11-116

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Abstract

BackgroundSeveral studies have indicated that human pre-implantation embryo-derived chorionic gonadotropin (hCG) may influence the implantation process by its action on human endometrial epithelial and stromal cells. Despite reports indicating that hCG acts on these cells to affect the production of several cytokines and growth factors (e.g., MIF, IGF-I, VEGF, LIF, IL-11, GMCSF, CXL10 and FGF2), our understanding of the integral influence of hCG on paracrine interactions between endometrial stromal and epithelial cells during implantation is very limited.MethodsIn the present study, we examined the profile of 48 cytokines in the conditioned media of primary cell cultures of human implantation stage endometrium. Endometrial epithelial cells (group 1; n = 20), stromal cells (group 2; n = 20), and epithelial plus stromal cells (group 3; n = 20) obtained from mid-secretory stage endometrial samples (n = 60) were grown on collagen and exposed to different doses (0, 1, 10 and 100 IU/ml) of rhCG for 24 h in vitro. Immunochemical and qRT-PCR methods were used to determine cytokine profiles. Enrichment and process networks analyses were implemented using a list of cytokines showing differential secretion in response to hCG.ResultsUnder basal conditions, endometrial epithelial and stromal cells exhibited cell type-specific profiles of secreted cytokines. Administration of hCG (100 IU) resulted in significantly (P < 0.05) different cytokine secretion profiles indicative of macropinocytic transport (HGF, MCSF) in epithelial cells, signal transduction (CCL4, FGF2, IL-1b, IL-6, IL-17, VEGF) in stromal cells, and epithelial-mesenchymal transition (FGF2, HGF, IL-1b, TNF) in mixed cells. Overall, the administration of hCG affected cytokines involved in the immune response, chemotaxis, inflammatory changes, proliferation, cell adhesion and apoptosis.ConclusionsCG can influence the function of the endometrium during blastocyst implantation via its differential action on endometrial epithelial and stromal cells. CG may also affect complex paracrine processes in the different endometrial cell types.

Highlights

Several studies have indicated that human pre-implantation embryo-derived chorionic gonadotropin may influence the implantation process by its action on human endometrial epithelial and stromal cells
Paiva et al [14] examined the effect of human pre-implantation embryo-derived chorionic gonadotropin (hCG) (0.2, 2 and 20 IU/ml) administered to human endometrial epithelial cells in vitro and observed that recombinant hCG stimulated the secretion of six analytes (VEGF, LIF, IL-11, GMCSF, CXL10 and FGF2)
Despite the fact that there were several cytokines, chemokines and growth factors commonly secreted by isolated endometrial epithelial cells, stromal cells and mixed cells under basal conditions, there were many cytokines that were secreted by endometrial epithelial cells

Summary

Introduction

Several studies have indicated that human pre-implantation embryo-derived chorionic gonadotropin (hCG) may influence the implantation process by its action on human endometrial epithelial and stromal cells. Despite reports indicating that hCG acts on these cells to affect the production of several cytokines and growth factors (e.g., MIF, IGF-I, VEGF, LIF, IL-11, GMCSF, CXL10 and FGF2), our understanding of the integral influence of hCG on paracrine interactions between endometrial stromal and epithelial cells during implantation is very limited. We addressed these issues through the multi-analyte profiling of 48 cytokines, chemokines and growth factors The secretion of these factors was assessed in the conditioned media of threedimensional primary cell cultures of human endometrial epithelial cells, stromal cells, and epithelial plus stromal cells isolated from endometrial biopsies collected during the ‘window’ of implantation. The cytokines, chemokines and growth factors investigated in the study have been previously reported to be synthesised and secreted by the human endometrium [21]

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