Endometrial cytokines in patients with and without endometriosis evaluated for infertility

Jørgensen, Hilde; Fedorcsák, Péter; Isaacson, Keith; Tevonian, Erin; Xiao, A.M.; Beste, Michael T.; Qvigstad, Erik; Lauffenburger, Douglas A.; Griffith, Linda G.

doi:10.1016/j.fertnstert.2021.11.024

Cited by 13 publications

(9 citation statements)

References 88 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, it is plausible that a lack of decidualizing endometrial stromal cells (with concomitant reduced production of IL-15 and uNK chemo attractants) reduces the infiltration and proliferation of uNK in decidualizing zones. Defective uNK cell function has recently been proposed in the setting of endometriosis with infertility [ 127 ]. We did not observe IL15 expression by ME-stromal cells; this is not surprising as IL-15 expression by stromal cells peaks before the mid-secretory phase.…”

Section: Discussionmentioning

confidence: 99%

Single-cell analysis of menstrual endometrial tissues defines phenotypes associated with endometriosis

Shih

Adelson

Vashistha

et al. 2022

BMC Med

View full text Add to dashboard Cite

Background Endometriosis is a common, complex disorder which is underrecognized and subject to prolonged delays in diagnosis. It is accompanied by significant changes in the eutopic endometrial lining. Methods We have undertaken the first single-cell RNA-sequencing (scRNA-Seq) comparison of endometrial tissues in freshly collected menstrual effluent (ME) from 33 subjects, including confirmed endometriosis patients (cases) and controls as well as symptomatic subjects (who have chronic symptoms suggestive of endometriosis but have not been diagnosed). Results We identify a unique subcluster of proliferating uterine natural killer (uNK) cells in ME-tissues from controls that is almost absent from endometriosis cases, along with a striking reduction of total uNK cells in the ME of cases (p < 10−16). In addition, an IGFBP1+ decidualized subset of endometrial stromal cells are abundant in the shed endometrium of controls when compared to cases (p < 10−16) confirming findings of compromised decidualization of cultured stromal cells from cases. By contrast, endometrial stromal cells from cases are enriched in cells expressing pro-inflammatory and senescent phenotypes. An enrichment of B cells in the cases (p = 5.8 × 10−6) raises the possibility that some may have chronic endometritis, a disorder which predisposes to endometriosis. Conclusions We propose that characterization of endometrial tissues in ME will provide an effective screening tool for identifying endometriosis in patients with chronic symptoms suggestive of this disorder. This constitutes a major advance, since delayed diagnosis for many years is a major clinical problem in the evaluation of these patients. Comprehensive analysis of ME is expected to lead to new diagnostic and therapeutic approaches to endometriosis and other associated reproductive disorders such as female infertility.

show abstract

Section: Discussionmentioning

confidence: 99%

Single-cell analysis of menstrual endometrial tissues defines phenotypes associated with endometriosis

Shih

Adelson

Vashistha

et al. 2022

BMC Med

View full text Add to dashboard Cite

show abstract

“…There may be a hereditable component of the disease given that first-degree relatives of women with endometriosis have a six times greater risk of presentation compared to unaffected counterparts (Simpson et al, 1980) and genetic linkage studies have identified specific gene variants highly associated with disease (Tapmeier et al, 2021). Reports of molecular differences in the endometria of women with endometriosis compared to controls (Prašnikar et al, 2020) remain controversial (McKinnon et al, 2018), and such comparisons may require stratification to subpopulations of patients to be effective (Jørgensen, H.;Fedorcsak, P.;Isaacson, K.;Tevonian, E.;Xiao, A.;Beste, M.;Qvigstad, E.;Lauffenburger, D.;Griffith, 2022). One well characterized feature of endometriosis pathology is its response, or lack of response, to sex hormones; endometriosis is an estrogen dependent (Bulun, 2009), but progesterone resistant, disease (Burney et al, 2007).…”

Section: Summary 1 Introductionmentioning

confidence: 99%

Integrating endometrial proteomic and single cell transcriptomic pipelines reveals distinct menstrual cycle and endometriosis-associated molecular profiles

Baugh

Goods

Gnecco

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Endometriosis is a debilitating gynecological disorder affecting approximately 10% of the female population. Despite its prevalence, robust methods to classify and treat endometriosis remain elusive. Changes throughout the menstrual cycle in tissue size, architecture, cellular composition, and individual cell phenotypes make it extraordinarily challenging to identify markers or cell types associated with uterine pathologies since disease-state alterations in gene and protein expression are convoluted with cycle phase variations. Here, we developed an integrated workflow to generate both proteomic and single–cell RNA–sequencing (scRNA–seq) data sets using tissues and cells isolated from the uteri of control and endometriotic donors. Using a linear mixed effect model (LMM), we identified proteins associated with cycle stage and disease, revealing a set of genes that drive separation across these two biological variables. Further, we analyzed our scRNA–seq data to identify cell types expressing cycle and disease–associated genes identified in our proteomic data. A module scoring approach was used to identify cell types driving the enrichment of certain biological pathways, revealing several pathways of interest across different cell subpopulations. Finally, we identified ligand–receptor pairs including Axl/Tyro3 – Gas6, that may modulate interactions between endometrial macrophages and/or endometrial stromal/epithelial cells. Analysis of these signaling pathways in an independent cohort of endometrial biopsies revealed a significant decrease in Tyro3 expression in patients with endometriosis compared to controls, both transcriptionally and through histological staining. This measured decrease in Tryo3 in patients with disease could serve as a novel diagnostic biomarker or treatment avenue for patients with endometriosis. Taken together, this integrated approach provides a framework for integrating LMMs, proteomic and RNA–seq data to deconvolve the complexities of complex uterine diseases and identify novel genes and pathways underlying endometriosis.

show abstract

“…However, it is plausible that a lack of decidualizing endometrial stromal cells (with concomitant reduced production of IL-15 and uNK chemoattractants) reduces the infiltration and proliferation of uNK in decidualizing zones. Defective uNK cell function has recently been proposed in the setting of endometriosis with infertility (129). We did not observe IL15 expression by ME-stromal cells; this is not surprising as IL-15 expression by stromal cells peaks before the mid-secretory phase.…”

Section: Discussionmentioning

confidence: 99%

Single cell analysis of menstrual endometrial tissues defines phenotypes associated with endometriosis

Shih

Adelson

Vashistha

et al. 2022

Preprint

View full text Add to dashboard Cite

Background. Endometriosis is a common, complex disorder which is under-recognized and subject to prolong delays in diagnosis. It is accompanied by significant changes in the eutopic endometrial lining. Methods. We have undertaken the first single cell RNA-sequencing (scRNA-Seq) comparison of endometrial tissues in freshly collected menstrual effluent (ME) from 33 subjects, including confirmed endometriosis patients (cases) and controls as well as symptomatic subjects. Results. We identify a unique subcluster of proliferating uterine natural killer (uNK) cells in ME-tissues from controls that is almost absent from endometriosis cases, along with a striking reduction of total uNK cells in the ME of cases (p<10-16). In addition, IGFBP1+ decidualized subset of stromal cells are abundant in the shed endometrium of controls when compared to cases (p<10-16) confirming findings of compromised decidualization of cultured stromal cells from cases. By contrast, endometrial stromal cells from cases are enriched in cells expressing a pro-inflammatory phenotype. An enrichment of B cells in the cases (p=5.8 x 10-6) raises the possibility in some subjects of chronic endometritis, a disorder which predisposes to endometriosis. Conclusions. We propose that characterization of endometrial tissues in ME will provide an effective screening tool for identifying endometriosis in patients with chronic symptoms suggestive of this disorder. This constitutes a major advance, since delayed diagnosis for many years is a major clinical problem in the evaluation of these patients. Comprehensive analysis of ME is expected to lead to new diagnostic and therapeutic approaches to endometriosis and other associated reproductive disorders such as female infertility.

show abstract

Endometrial cytokines in patients with and without endometriosis evaluated for infertility

Cited by 13 publications

References 88 publications

Single-cell analysis of menstrual endometrial tissues defines phenotypes associated with endometriosis

Single-cell analysis of menstrual endometrial tissues defines phenotypes associated with endometriosis

Integrating endometrial proteomic and single cell transcriptomic pipelines reveals distinct menstrual cycle and endometriosis-associated molecular profiles

Single cell analysis of menstrual endometrial tissues defines phenotypes associated with endometriosis

Contact Info

Product

Resources

About