Extracellular vesicles secreted by adenomyosis endometrial organoids contain miRNAs involved in embryo implantation and pregnancy

Juárez‐Barber, Elena; Segura-Benítez, Marina; Carbajo-García, María Cristina; Bas-Rivas, Alba; Faus, Amparo; Vidal, Carmen; Gilés, Juan; Labarta, Elena; Pellicer, A.; Cervelló, Irene; Ferrero, Hortensia

doi:10.1016/j.rbmo.2022.12.008

Cited by 9 publications

(6 citation statements)

References 105 publications

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“…As high MTRNR2L1 expression in human endometrium is highly specific to endometrial epithelial glandular cells (50), the lower expression of this gene in endometriosis patients might be driven either by lower expression levels in their epithelial cells, or by a proportion of epithelial cells present in their MF. Interestingly, despite not having been previously linked to endometriosis, MTRNR2L1 was found to be downregulated in the eutopic endometrium of adenomyosis patients compared to healthy controls (51).…”

Section: Resultsmentioning

confidence: 91%

Single-cell characterization of menstrual fluid at homeostasis and in endometriosis

Schwalie,

Bafligil,

Russeil

et al. 2024

Preprint

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Progress in detecting and understanding endometrial conditions in women of fertile age, such as endometriosis, has been hampered by the invasiveness of the sample collection procedure. Menstrual fluid (MF) can be sampled non-invasively and could provide a unique opportunity to study the physiological state of tissues in the reproductive system. Despite this potential, the use of MF for diagnostics and research has been limited. Here we establish protocols and assess the feasibility of collecting and processing MF in an outpatient setting. We characterize the cellular contents of MF from 15 healthy women using flow cytometry and single-cell RNA-sequencing, and demonstrate the ability to recover millions of live cells from the different cellular fractions of interest (epithelial, stromal, endothelial, perivascular and blood). Through computational integration of MF with endometrial samples we show that MF sampling is a good surrogate for endometrial biopsy. In a proof-of-principle case-control study, we collect MF from a further 7 women with a diagnosis of endometriosis and 11 healthy controls. Through RNA sequencing of 93 MF samples from these women we highlight important differences between ex vivo and cultured cells, identify impaired decidualisation, low apoptosis, high proliferation, and both higher and lower inflammatory activity in different subsets of immune cells as distinguishing features of endometriosis patients. Finally, we identify potential novel pan-cell-type biomarkers for this neglected condition.

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Section: Resultsmentioning

confidence: 91%

Single-cell characterization of menstrual fluid at homeostasis and in endometriosis

Schwalie,

Bafligil,

Russeil

et al. 2024

Preprint

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“…They identified several miRNAs contained within the EVs that may promote implantation failure, including hsa-miR-24-3p and hsa-miR-423-5p, which have been associated with inhibiting trophoblast invasion. Additionally, they found hsa-miR-21-5p and hsa-miR-320a-3p, which are related to recurrent implantation failure [87].…”

Section: Adenomyosismentioning

confidence: 99%

Role of Endometrial Extracellular Vesicles in Mediating Cell-to-Cell Communication in the Uterus: A Review

Beal,

Ma,

Bagchi

et al. 2023

Cells

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There are several critical events that occur in the uterus during early pregnancy which are necessary for the establishment and maintenance of pregnancy. These events include blastocyst implantation, uterine decidualization, uterine neoangiogenesis, differentiation of trophoblast stem cells into different trophoblast cell lineages, and formation of a placenta. These processes involve several different cell types within the pregnant uterus. Communication between these cell types must be intricately coordinated for successful embryo implantation and the formation of a functional maternal–fetal interface in the placenta. Understanding how this intricate coordination transpires has been a focus of researchers in the field for many years. It has long been understood that maternal endometrial tissue plays a key role in intercellular signaling during early pregnancy, sending signals to nearby tissues in a paracrine manner. Recently, insights have been obtained into the mechanisms by which these signaling events occur. Notably, the endometrium has been shown to secrete extracellular vesicles (EVs) that contain crucial cargo (proteins, lipids, RNA, miRNA) that are taken up by recipient cells to initiate a response leading to the occurrence of critical events during implantation and placentation. In this review, we aim to summarize the role that endometrium-derived EVs play in mediating cell-to-cell communications within the pregnant uterus to orchestrate the events that must occur to establish and maintain pregnancy. We will also discuss how aberrant endometrial EV signaling may lead to pathophysiological conditions, such as endometriosis and infertility.

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“…Protein cargos of sEVs derived from endometrial epithelial cells enhance the adhesive capacity of trophoblast, potentially contributing to embryo implantation ( 73 ). Intriguingly, in patients with adenomyosis (a condition where endometrial-like cells grow into the myometrium causing heavy menstrual bleeding, pain and infertility, often in association with endometriosis) ( 74 ), sEVs secreted by endometrial organoids contain miRNAs associated with pregnancy complications and adenomyosis progression ( 75 ).…”

Section: Small Extracellular Vesicle-mediated Crosstalk In Tissue-spe...mentioning

confidence: 99%

Macrophages and small extracellular vesicle mediated-intracellular communication in the peritoneal microenvironment: Impact on endometriosis development

Wang

Dragovic

Greaves

et al. 2023

Front. Reprod. Health

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Endometriosis is an inflammatory disease that is defined as the growth of endometrium-like tissue outside the uterus, commonly on the lining of the pelvic cavity, visceral organs and in the ovaries. It affects around 190 million women of reproductive age worldwide and is associated with chronic pelvic pain and infertility, which greatly impairs health-related life quality. The symptoms of the disease are variable, this combined with a lack of diagnostic biomarkers and necessity of surgical visualisation to confirm disease, the prognosis can take an average timespan of 6–8 years. Accurate non-invasive diagnostic tests and the identification of effective therapeutic targets are essential for disease management. To achieve this, one of the priorities is to define the underlying pathophysiological mechanisms that contribute to endometriosis. Recently, immune dysregulation in the peritoneal cavity has been linked to endometriosis progression. Macrophages account for over 50% of immune cells in the peritoneal fluid and are critical for lesion growth, angiogenesis, innervation and immune regulation. Apart from the secretion of soluble factors like cytokines and chemokines, macrophages can communicate with other cells and prime disease microenvironments, such as the tumour microenvironment, via the secretion of small extracellular vesicles (sEVs). The sEV-mediated intracellular communication pathways between macrophages and other cells within the peritoneal microenvironment in endometriosis remain unclear. Here, we give an overview of peritoneal macrophage (pMΦ) phenotypes in endometriosis and discuss the role of sEVs in the intracellular communication within disease microenvironments and the impact they may have on endometriosis progression.

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Extracellular vesicles secreted by adenomyosis endometrial organoids contain miRNAs involved in embryo implantation and pregnancy

Cited by 9 publications

References 105 publications

Single-cell characterization of menstrual fluid at homeostasis and in endometriosis

Single-cell characterization of menstrual fluid at homeostasis and in endometriosis

Role of Endometrial Extracellular Vesicles in Mediating Cell-to-Cell Communication in the Uterus: A Review

Macrophages and small extracellular vesicle mediated-intracellular communication in the peritoneal microenvironment: Impact on endometriosis development

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