Objective: To establish a model of human implantation that responds to hormonal stimuli and can differentiate between endometrium from fertile women and those with idiopathic infertility.

Design: A trophoblast stem cell (trophectodermal) line (TSC; derived from human pre-implantation embryo) was used to form trophectodermal spheroids (TS). TS attachment to monolayers of endometrial epithelial cell lines or primary endometrial epithelial cells (pHEECs) was determined.

Setting: Independent Medical Research Institute with close clinical linkages INTERVENTIONS: Spheroid attachment and outgrowth was determined with added hormones (estradiol 17β (E), E + medroxyprogesterone acetate (MPA) or E + MPA + human chorionic gonadotropin (hCG)). Spheroid attachment to E/MPA treated pHEEC prepared from fertile women or those with idiopathic infertility tested.

Main Outcome Measure: Firmly attached spheroids counted after co-culture for 6 h. Outgrowth was determined by quantitation of area covered by spheroid after firm adhesion.

Results: Functional adhesion of TS to two endometrial epithelial cell lines, Ishikawa and ECC-1 cells, was hormonally responsive, with adhesion/outgrowth increased by E/MPA (ECC-1; p < 0.01, Ishikawa; p < 0.01) and E/MPA/hCG (ECC-1; p < 0.001, Ishikawa p < 0.01) versus E alone. The same pattern of hormone responsiveness was observed in pHEEC obtained from fertile women (E vs, E/MPA; p < 0.01, E vs. E/MPA/hCG; p < 0.001). TS adhered to 85% of pHEEC obtained from fertile women (11/13) and 11% of pHEEC obtained from women with unexplained infertility (2/18, p < 0.001).

Conclusion: This new model of "embryo" implantation largely discriminates between endometrial epithelial cells obtained from fertile vs. infertile women based on adhesion; this holds potential as an in vitro "diagnostic" tool of endometrial infertility.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000590PMC
http://dx.doi.org/10.1007/s10815-019-01629-0DOI Listing

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