Single-cell mapping of human endometrium and decidua reveals epithelial and stromal contributions to fertility

TL;DR

This study maps gene activity in the human endometrium to identify key changes in epithelial and stromal cells that support embryo implantation and fertility.

Contribution

The study identifies a novel gene expression signature (GERM) linked to endometrial receptivity and reveals epithelial and stromal changes during implantation.

Findings

A gene expression signature called GERM is associated with endometrial receptivity during the mid-secretory phase.

Epithelial and stromal cell changes are critical for embryo implantation and are disrupted in cases of impaired fertility.

The study provides a detailed transcriptomic atlas of the receptive endometrium and early pregnancy.

Abstract

The human endometrium undergoes dynamic changes across the menstrual cycle to establish a receptive state for embryo implantation. Using bulk and single-cell RNA-Seq, we characterized gene expression dynamics in the cycling endometrium and the decidua from early pregnancy. We demonstrated that during the mid-secretory phase — the period encompassing the window of implantation — secretory glandular epithelial cells undergo notable transcriptional changes and alterations in cell-cell communication. Through comprehensive analyses, we identified the glandular epithelium receptivity module (GERM) signature, comprising 556 genes associated with endometrial receptivity. This GERM signature was consistently perturbed across datasets of endometrial samples from women with impaired fertility, validating its relevance as a marker of receptivity. In addition to epithelial changes, we observed shifts in stromal cell populations, notably involving decidual and senescent subsets, which also play key roles in modulating implantation. Together, these findings provide a high-resolution transcriptomic atlas of the receptive and early pregnant endometrium and shed light on key molecular pathways underlying successful implantation.

This study reveals critical endometrial gene expression shifts, identifying a unique epithelial receptivity signature and stromal changes that support embryo implantation, and highlighting fertility-related disruptions.

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