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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 2

Expression of ESR1 and PGR in secretory phase endometrium and first trimester decidua.

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Expression of ESR1 and PGR in secretory phase endometrium and first trim...
(A and B) Violin plots showing the expression of ESR1 (A) and PGR (B) in the stromal and epithelial clusters across the secretory phase and in first trimester decidua. (C and D) Representative images of endometrial tissue sections stained to detect expression of ESR1 (C) and PGR (D) in glands and stroma of early, mid-, and late secretory phase endometrium and endometrial decidua of first trimester pregnancy. G, gland; red arrowheads identify the luminal epithelium. Scale bars: 10 μm.

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