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Single-cell mapping of human endometrium and decidua reveals epithelial and stromal contributions to fertility
Gregory W. Burns, Emmanuel N. Paul, Manisha Persaud, Qingshi Zhao, Rong Li, Kristin Blackledge, Jessica Garcia de Paredes, Pratibha Shukla, Ripla Arora, Anat Chemerinski, Nataki C. Douglas
Gregory W. Burns, Emmanuel N. Paul, Manisha Persaud, Qingshi Zhao, Rong Li, Kristin Blackledge, Jessica Garcia de Paredes, Pratibha Shukla, Ripla Arora, Anat Chemerinski, Nataki C. Douglas
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Research Article Cell biology Reproductive biology

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

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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.

Authors

Gregory W. Burns, Emmanuel N. Paul, Manisha Persaud, Qingshi Zhao, Rong Li, Kristin Blackledge, Jessica Garcia de Paredes, Pratibha Shukla, Ripla Arora, Anat Chemerinski, Nataki C. Douglas

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Figure 6

Cluster identification and communication in the stroma.

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Cluster identification and communication in the stroma.
(A) Dot plot of ...
(A) Dot plot of in vitro senescence markers across stages. (B) Dot plot of SCARA5 and DIO2, in vivo markers for decidualization and senescence, respectively. (C) Cell-cell communication of the stroma clusters. Edge colors are consistent with the sources as sender, and edge weights are proportional to the interaction strength; that is, a thicker line indicates a stronger signal. Circle sizes are proportional to the number of cells in each cluster. Communication in the early secretory (D), mid-secretory (E), and late secretory (F) phases, and first trimester decidua of pregnancy (G) are shown as heatmaps. Colored bars represent the relative signaling strength of pathways across subclusters. The top-colored bar plot represents the sum of each column of the absolute values displayed in the heatmap (incoming signaling). The right colored bar plot represents the sum of each row of the absolute values (outgoing signaling).

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