Proteomic Insights into Endometrial Receptivity and Embryo-Endometrial Epithelium Interaction for Implantation; Critical Determinants of Fertility.

Jemma Evans; Jennifer Hutchison; Lois A Salamonsen; David W Greening
In vitro fertilization has overcome infertility issues for many couples. However, achieving implantation of a viable embryo into the maternal endometrium remains a limiting step in optimizing pregnancy success. The molecular mechanisms which characterize the transient state of endometrial receptivity, critical in enabling embryo-endometrial interactions, and proteins which underpin adhesion at the implantation interface, are limited in humans despite these temporally regulated processes fundamental to life. Hence, failure of implantation remains the 'final frontier' in infertility. We utilized a human co-culture model utilizing spheroids of a trophectoderm (trophoblast stem) cell line, derived from pre-implantation human embryos, and primary human endometrial epithelial cells, to functionally identify 'fertile' versus 'infertile' endometrial epithelium based on adhesion between these cell types. Quantitative proteomics identified proteins associated with human endometrial epithelial receptivity ('epithelial receptome') and trophectoderm adhesion ('adhesome'). As validation, key 'epithelial receptome' proteins (MAGT-1/CDA/LGMN/KYNU/PC4) localized to the epithelium of receptive phase (mid-secretory) endometrium obtained from fertile, normally cycling women but were largely absent from non-receptive (proliferative) phase tissues. We demonstrate factors involved in embryo-epithelium interaction in successive temporal stages of endometrial receptivity and implantation and provide potential targets for improving fertility, enhancing potential to become pregnant either naturally or in a clinical setting. This article is protected by copyright. All rights reserved.
ISSN 1615-9861
Published 11 Dec 2019
Pages e1900250
DOI 10.1002/pmic.201900250
Type Journal Article