ArticleProceedings of the National Academy of Sciences of the United States of America2022
Extracellular vesicles secreted by human uterine stromal cells regulate decidualization, angiogenesis, and trophoblast differentiation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 68 citations in OpenAlex.
- Hyperadhesive von Willebrand Factor Contributes to Pathogenesis of Preeclampsia.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Metabolic Reprogramming at the Maternal-Fetal Interface: Insights from Decidual Stromal Cells and Trophoblasts in Healthy Pregnancy Versus Recurrent Pregnancy Loss.International journal of molecular sciences · 2026Review
- Deciphering the maternal uterine signals that shape placenta development.Reproduction (Cambridge, England) · 2026Review
- Extracellular vesicles in pregnancy-related disorders: from mechanisms to clinical implications.Science China. Life sciences · 2026Review
- Divergent Roles of HIF-1α and HIF-2α in Embryonic Development and Early Pregnancy.International journal of molecular sciences · 2026Review
- Decidualization-empowered ECM hydrogel integrating sustained Tβ4 release drives endometrial regeneration in intrauterine adhesions.Nature communications · 2026Article
- Maternal hyperhomocysteinemia induces fetal growth restriction by suppressing angiogenesis at the maternal-fetal interface.Cell & bioscience · 2026Article
- Reproductive fluids, commercial media, and organoids: bridging the gap in IVF culture systems.Human reproduction open · 2026Review
- Heat stress modulates extracellular vesicles miRNA cargo in bovine uterine fluid and uterine function.Frontiers in veterinary science · 2026Article
- Morpho-functional uterine and placental dynamics during establishment and maintenance of canine pregnancy, from early trophoblast invasion to parturition.The Journal of reproduction and development · 2026Review
- Progesterone modulates protein cargo in extracellular vesicles released from bovine uterine epithelial cells.Reproduction & fertility · 2026Article
- Extracellular Vesicles in Implantation: Cross-Talk Between the Embryo and Endometrium.Advances in anatomy, embryology, and cell biology · 2026Review
- Crosstalk of extracellular vesicles in maternal-fetal interaction.Frontiers in cell and developmental biology · 2026Review
- Atosiban-conjugated 3WJ-pRNA nanoparticles delivering GAS1-enhanced extracellular vesicles: targeting the decidua to combat recurrent miscarriage.Journal of nanobiotechnology · 2025Article
- Non-Invasive Extracellular Vesicle Biomarkers in Endometriosis, Molecular Signatures Linking Pelvic Inflammation, Oocyte Quality, and IVF OutcomesCurrent issues in molecular biology · 2025Review
- Extracellular vesicles in metabolic perspective: mechanism and targeted therapy.Journal of nanobiotechnology · 2025Review
- Decidualised endometrial stromal cell-derived extracellular vesicles induce bystander decidualisation and cAMP-mediated attenuation of natural killer cell cytotoxicity.Clinical and translational medicine · 2025Article
- Systematic review on the extracellular vesicles in reproductive medicine and gamete union.Journal of pharmaceutical analysis · 2025Review
- Human Decidual RUNX1 Promotes Angiogenesis and Trophoblast Differentiation by Regulating Extracellular Vesicle Signaling.Endocrinology · 2025Article
- Correlation of VEGF, HIF-1α, and MMP2 expression in placental villi among patients with recurrent spontaneous abortion.Obstetrics & gynecology science · 2025Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
In humans, the uterus undergoes a dramatic transformation to form an endometrial stroma-derived secretory tissue, termed decidua, during early pregnancy. The decidua secretes various factors that act in an autocrine/paracrine manner to promote stromal differentiation, facilitate maternal angiogenesis, and influence trophoblast differentiation and development, which are critical for the formation of a functional placenta. Here, we investigated the mechanisms by which decidual cells communicate with each other and with other cell types within the uterine milieu. We discovered that primary human endometrial stromal cells (HESCs) secrete extracellular vesicles (EVs) during decidualization and that this process is controlled by a conserved HIF2α-RAB27B pathway. Mass spectrometry revealed that the decidual EVs harbor a variety of protein cargo, including cell signaling molecules, growth modulators, metabolic regulators, and factors controlling endothelial cell expansion and remodeling. We tested the hypothesis that EVs secreted by the decidual cells mediate functional communications between various cell types within the uterus. We demonstrated that the internalization of EVs, specifically those carrying the glucose transporter 1 (GLUT1), promotes glucose uptake in recipient HESCs, supporting and advancing the decidualization program. Additionally, delivery of HESC-derived EVs into human endothelial cells stimulated their proliferation and led to enhanced vascular network formation. Strikingly, stromal EVs also promoted the differentiation of trophoblast stem cells into the extravillous trophoblast lineage. Collectively, these findings provide a deeper understanding of the pleiotropic roles played by EVs secreted by the decidual cells to ensure coordination of endometrial differentiation and angiogenesis with trophoblast function during the progressive phases of decidualization and placentation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.