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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 9

Disrupted stromal cell populations and epithelial gene expression in patients with infertility.

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Disrupted stromal cell populations and epithelial gene expression in pat...
(A) Dot plot of SCARA5, DIO2, FOS, and CXCL14 for identification of the stroma populations in control endometrium samples from an scRNA-Seq dataset (GSE183837). (B) Stacked bar plot shows altered stroma cell proportions in endometrial samples from patients with recurrent implantation failure (RIF). (C) GERM upregulated genes in the secretory glandular epithelium are reduced in patients with RIF. (D) GERM score is positively correlated with mid-secretory endometrium from control patients (GSE132711, n = 11; GSE234354, n = 81; GSE4888, n = 11) and endometrial epithelial organoids (EEO; GSE136795, n = 6), but not from patients with unexplained infertility (UIF; GSE165004, n = 48), recurrent pregnancy loss (RPL; GSE165004, n = 48 and GSE183555, n = 10), or RIF (GSE284236, n = 16 and GSE183837, n = 9). A gray circle indicates an insignificant combined P value (p.meta) ≥ 0.05.

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