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• W2596133086 abstract "Successful blastocyst implantation requires a synchronized dialogue between a receptive endometrium and a functional blastocyst. This is mediated in part by endometrial cytokines/growth factors secreted by glandular epithelium into the uterine cavity, which may contribute to endometrial receptivity and also support the blastocyst during implantation. Recent evidence suggests that blastocyst-derived hCG may further influence the endometrial milieu in conception cycles to enhance receptivity. The inability to achieve endometrial receptivity results in infertility in women and contributes to the failure of reproductive technologies. However, there is currently no robust test for endometrial receptivity, which can inform clinical decisions. This study aimed to investigate the profiles of a selected cohort of 42 cytokines/growth factors in human uterine fluid and secreted by primary human endometrial epithelial cells (hEECs). These factors included those with known and unknown roles in receptivity and implantation. The association between these factors and endometrial receptivity and infertility and the effect of hCG on their production by primary hEEC was also investigated. Uterine fluid (collected by flushing the uterine cavity with 5 ml saline) was obtained from fertile women during the receptive (mid-secretory phase; n=7) and non-receptive (mid-proliferative n=7) phases of the cycle, and from women with unexplained infertility during the receptive phase (n=9). hEECs isolated from endometrial biopsies collected from fertile cycling women (n=15), were treated under serum-free conditions ± recombinant hCG (0.2-20 IU/ml) for 48 hr. Uterine fluid and conditioned media from primary hEEC were analyzed using quantitative Milliplex Luminex cytokine assays. Both uterine fluid and primary hEEC conditioned media exhibited a remarkably similar cytokine profile. Over 30 cytokines/growth factors were identified, quantified and grouped according to their concentration ranges (from<1 to >1000 pg/ml). 8 factors including PDGFA, TNFB, sIL2RA, FLT3L, sCD40L, IL7 and IFNA2 were previously unknown in the endometrium. Comparison of uterine fluid from fertile non-receptive / receptive phase and infertile receptive phase cohorts revealed VEGF as significantly reduced (84%) in infertile compared to fertile cohorts (p<0.05). hCG (2 IU/ml) significantly increased the secretion of 6 factors including those with roles in receptivity and trophoblast function (IL11; 32±12%), blastocyst/trophoblast migration and adhesion (CXCL10; 31±11%), blastocyst development (GMCSF; 45±12%) and one with previously unknown roles in receptivity and implantation (FGF2; 52±23%)(p<0.05). Upregulation of known hCG-regulated proteins, VEGF and LIF, validated the study. Functional studies revealed that FGF2 (100ng/ml) stimulated phosphorylation of ERK1/2 in hEEC and both FGF2 and VEGF (100 ng/ml) stimulated hEEC adhesion to fibronectin (362±21%; 409±10%) and collagen type IV (391±64%; 513±15%) characteristic of blastocyst/trophectoderm-ECM (p<0.001; n=3). These findings indicate that soluble mediators in uterine secretions are derived from epithelial cells and support roles for hCG, VEGF and FGF2 in the molecular cross-talk important for endometrial receptivity and implantation. Identifying soluble mediators in uterine secretions may provide potential biomarkers of endometrial receptivity and insight into the unique microenvironment essential for the establishment of pregnancy. (platform)" @default.
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• W2596133086 date "2010-11-01" @default.
• W2596133086 modified "2023-10-18" @default.
• W2596133086 title "Regulatory Factors in Secretory Phase Uterine Washings Are Derived from Endometrial Epithelial Cells and Can Be Selectively Altered by hCG, Providing a Means to Enhance Receptivity." @default.
• W2596133086 doi "https://doi.org/10.1093/biolreprod/83.s1.14" @default.
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