# Back to the Future—A 50-Year Dive into Embryo Implantation Research: Cell Biological Paradox, Epithelial Cell Polarity, and EMT

## TL;DR

This paper reviews 50 years of research on embryo implantation, focusing on how epithelial cell polarity and partial changes in cell behavior enable successful implantation.

## Contribution

The paper highlights the role of partial epithelial-mesenchymal transition (EMT) in embryo implantation, offering new insights into its regulation.

## Key findings

- Trophoblast and uterine epithelium do not undergo complete EMT but use partial changes in epithelial programs.
- Recent data may help identify the exact changes and regulation mechanisms involved in implantation.
- Comparisons with epithelial fusion and tumor invasion provide useful insights into implantation processes.

## Abstract

Embryo implantation presents a cell biological paradox: contact formation between the trophoblast of the blastocyst and the epithelial lining of the endometrium contradicts typical epithelial cell behaviour, as does the subsequent invasion needed for placenta formation in most species (including the human). Explaining this conundrum became a challenge for investigation since its recognition about 40 years ago and it receives increasing interest because implantation failure appears to be a major cause for low success in assisted reproduction. The present article reviews the main findings that have directed attention of researchers on epithelial cell polarity and on the theoretical concept of epithelial–mesenchymal transition (EMT). Apart from trophoblast attachment competence, a special focus is on endometrial receptivity. Comparison with epithelial fusion processes (EFPs) in development and with tumour cell invasion has been and is still considered helpful in order to take advantage of the progress made in those fields. Concerning the mechanisms involved, it must be emphasized that trophoblast and uterine luminal epithelium (ULE) do not undergo a complete switch to a mesenchymal programme (do not undergo a complete EMT) but make use of partial changes in the epithelial programme. The large number of data accumulated recently should allow us to now make progress in identifying what these partial programme changes are exactly and how they are regulated; also, they may offer chances for obtaining deeper insights into the regulation of implantation.