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A novel “embryo-endometrial” adhesion model can potentially predict “receptive” or “non-receptive” endometrium

  • Reproductive Physiology and Disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

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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Acknowledgments

We thank the patients who gave their consent for this study and Sister Judi Hocking for collecting human tissue samples. We thank Prof Susan Fisher for her kind gift of TSC trophectodermal cells.

Funding

This work was supported by National Health and Medical Research Council of Australia project #1139489 and #1141946 and the Victorian Governments Operational Infrastructure funding. JE supported by a fielding foundation fellowship, Society for Reproductive Investigation Bridge grant, and NHMRC project grant. MB supported by the Ovarian Cancer Research Foundation (OCRF), Fielding Foundation Innovation Award, and the CASS foundation. LAS supported by the Hudson Institute of Medical Research.

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Authors and Affiliations

  1. The Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, VIC, 3168, Australia

    Jemma Evans, Kathryn J. Walker, Maree Bilandzic, Sophie Kinnear & Lois A. Salamonsen

  2. Department of Molecular and Translational Science, Monash University, Clayton, VIC, 3168, Australia

    Jemma Evans, Maree Bilandzic & Lois A. Salamonsen

  3. Department of Medicine, Monash University, Clayton, VIC, 3800, Australia

    Sophie Kinnear

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  1. Jemma Evans
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  2. Kathryn J. Walker
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  3. Maree Bilandzic
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  4. Sophie Kinnear
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  5. Lois A. Salamonsen
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Contributions

JE conceived the project, performed experimental work, performed data analysis, and wrote the manuscript. KJW and SK performed experimental work. MB helped with model development. LAS helped develop project, wrote, and edited manuscript and provided critical insight.

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Correspondence to Jemma Evans.

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Evans, J., Walker, K.J., Bilandzic, M. et al. A novel “embryo-endometrial” adhesion model can potentially predict “receptive” or “non-receptive” endometrium. J Assist Reprod Genet 37, 5–16 (2020). https://doi.org/10.1007/s10815-019-01629-0

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