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Nature Nov 2018During early human pregnancy the uterine mucosa transforms into the decidua, into which the fetal placenta implants and where placental trophoblast cells intermingle and...
During early human pregnancy the uterine mucosa transforms into the decidua, into which the fetal placenta implants and where placental trophoblast cells intermingle and communicate with maternal cells. Trophoblast-decidual interactions underlie common diseases of pregnancy, including pre-eclampsia and stillbirth. Here we profile the transcriptomes of about 70,000 single cells from first-trimester placentas with matched maternal blood and decidual cells. The cellular composition of human decidua reveals subsets of perivascular and stromal cells that are located in distinct decidual layers. There are three major subsets of decidual natural killer cells that have distinctive immunomodulatory and chemokine profiles. We develop a repository of ligand-receptor complexes and a statistical tool to predict the cell-type specificity of cell-cell communication via these molecular interactions. Our data identify many regulatory interactions that prevent harmful innate or adaptive immune responses in this environment. Our single-cell atlas of the maternal-fetal interface reveals the cellular organization of the decidua and placenta, and the interactions that are critical for placentation and reproductive success.
Topics: Cell Communication; Cell Differentiation; Decidua; Female; Fetus; Histocompatibility, Maternal-Fetal; Humans; Killer Cells, Natural; Ligands; Placenta; Pregnancy; RNA, Small Cytoplasmic; Sequence Analysis, RNA; Single-Cell Analysis; Stromal Cells; Transcriptome; Trophoblasts
PubMed: 30429548
DOI: 10.1038/s41586-018-0698-6 -
Nature Apr 2023The relationship between the human placenta-the extraembryonic organ made by the fetus, and the decidua-the mucosal layer of the uterus, is essential to nurture and...
The relationship between the human placenta-the extraembryonic organ made by the fetus, and the decidua-the mucosal layer of the uterus, is essential to nurture and protect the fetus during pregnancy. Extravillous trophoblast cells (EVTs) derived from placental villi infiltrate the decidua, transforming the maternal arteries into high-conductance vessels. Defects in trophoblast invasion and arterial transformation established during early pregnancy underlie common pregnancy disorders such as pre-eclampsia. Here we have generated a spatially resolved multiomics single-cell atlas of the entire human maternal-fetal interface including the myometrium, which enables us to resolve the full trajectory of trophoblast differentiation. We have used this cellular map to infer the possible transcription factors mediating EVT invasion and show that they are preserved in in vitro models of EVT differentiation from primary trophoblast organoids and trophoblast stem cells. We define the transcriptomes of the final cell states of trophoblast invasion: placental bed giant cells (fused multinucleated EVTs) and endovascular EVTs (which form plugs inside the maternal arteries). We predict the cell-cell communication events contributing to trophoblast invasion and placental bed giant cell formation, and model the dual role of interstitial EVTs and endovascular EVTs in mediating arterial transformation during early pregnancy. Together, our data provide a comprehensive analysis of postimplantation trophoblast differentiation that can be used to inform the design of experimental models of the human placenta in early pregnancy.
Topics: Female; Humans; Pregnancy; Cell Movement; Multiomics; Placenta; Pregnancy Trimester, First; Trophoblasts; Decidua; Maternal-Fetal Relations; Single-Cell Analysis; Myometrium; Cell Differentiation; Organoids; Stem Cells; Transcriptome; Transcription Factors; Cell Communication
PubMed: 36991123
DOI: 10.1038/s41586-023-05869-0 -
Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium.Nature Cell Biology May 2017In humans, the endometrium, the uterine mucosal lining, undergoes dynamic changes throughout the menstrual cycle and pregnancy. Despite the importance of the endometrium...
In humans, the endometrium, the uterine mucosal lining, undergoes dynamic changes throughout the menstrual cycle and pregnancy. Despite the importance of the endometrium as the site of implantation and nutritional support for the conceptus, there are no long-term culture systems that recapitulate endometrial function in vitro. We adapted conditions used to establish human adult stem-cell-derived organoid cultures to generate three-dimensional cultures of normal and decidualized human endometrium. These organoids expand long-term, are genetically stable and differentiate following treatment with reproductive hormones. Single cells from both endometrium and decidua can generate a fully functional organoid. Transcript analysis confirmed great similarity between organoids and the primary tissue of origin. On exposure to pregnancy signals, endometrial organoids develop characteristics of early pregnancy. We also derived organoids from malignant endometrium, and so provide a foundation to study common diseases, such as endometriosis and endometrial cancer, as well as the physiology of early gestation.
Topics: Adult Stem Cells; Cell Culture Techniques; Cell Differentiation; Cell Lineage; Cell Proliferation; Cells, Cultured; Culture Media; Decidua; Endometrial Neoplasms; Endometrium; Estrogens; Female; Gene Expression Regulation, Developmental; Genotype; Humans; Organoids; Phenotype; Pregnancy; Progesterone; Time Factors; Tissue Engineering; Tumor Cells, Cultured
PubMed: 28394884
DOI: 10.1038/ncb3516 -
Cell Proliferation Nov 2021Successful pregnancy involves the homeostasis between maternal decidua and fetoplacental units, whose disruption contributes to compromised pregnancy outcomes, including...
OBJECTIVES
Successful pregnancy involves the homeostasis between maternal decidua and fetoplacental units, whose disruption contributes to compromised pregnancy outcomes, including recurrent spontaneous abortion (RSA). The role of cell heterogeneity of maternal decidua in RSA is yet to be illustrated.
MATERIALS AND METHODS
A total of 66,078 single cells from decidua samples isolated from patients with RSA and healthy controls were analysed by unbiased single-cell RNA sequencing (scRNA-seq).
RESULTS
Our scRNA-seq results revealed that stromal cells are the most abundant cell type in decidua during early pregnancy. RSA samples are accompanied by aberrant decidualization and obviously obstructed communication between stromal cells and other cell types, such as abnormal activation of macrophages and NK cells. In addition, the over-activated TNF superfamily member 12 (TNFSF12, TWEAK) and FASLG in RSA are closely related to stromal cell demise and pregnancy failure.
CONCLUSIONS
Our research reveals that the cell composition and communications in normal and RSA decidua at early pregnancy and provides insightful information for the pathology of RSA and will pave the way for pregnancy loss prevention.
Topics: Abortion, Habitual; Adult; Decidua; Female; Gene Expression Profiling; Humans; Killer Cells, Natural; Pregnancy; Single-Cell Analysis; Trophoblasts; Young Adult
PubMed: 34546587
DOI: 10.1111/cpr.13125 -
Frontiers in Immunology 2022Patients with recurrent pregnancy loss (RPL) account for approximately 1%-5% of women aiming to achieve childbirth. Although studies have shown that RPL is associated... (Review)
Review
Patients with recurrent pregnancy loss (RPL) account for approximately 1%-5% of women aiming to achieve childbirth. Although studies have shown that RPL is associated with failure of endometrial decidualization, placental dysfunction, and immune microenvironment disorder at the maternal-fetal interface, the exact pathogenesis remains unknown. With the development of high-throughput technology, more studies have focused on the genomics, transcriptomics, proteomics and metabolomics of RPL, and new gene mutations and new biomarkers of RPL have been discovered, providing an opportunity to explore the pathogenesis of RPL from different biological processes. Bioinformatics analyses of these differentially expressed genes, proteins and metabolites also reflect the biological pathways involved in RPL, laying a foundation for further research. In this review, we summarize the findings of omics studies investigating decidual tissue, villous tissue and blood from patients with RPL and identify some possible limitations of current studies.
Topics: Abortion, Habitual; Decidua; Endometrium; Female; Humans; Placenta; Pregnancy; Proteomics
PubMed: 35572542
DOI: 10.3389/fimmu.2022.826198 -
Science Advances Oct 2018The placenta and decidua interact dynamically to enable embryonic and fetal development. Here, we report single-cell RNA sequencing of 14,341 and 6754 cells from...
The placenta and decidua interact dynamically to enable embryonic and fetal development. Here, we report single-cell RNA sequencing of 14,341 and 6754 cells from first-trimester human placental villous and decidual tissues, respectively. Bioinformatic analysis identified major cell types, many known and some subtypes previously unknown in placental villi and decidual context. Further detailed analysis revealed proliferating subpopulations, enrichment of cell type-specific transcription factors, and putative intercellular communication in the fetomaternal microenvironment. This study provides a blueprint to further the understanding of the roles of these cells in the placenta and decidua for maintenance of early gestation as well as pathogenesis in pregnancy-related disorders.
Topics: Biomarkers; Chorionic Villi; Decidua; Female; High-Throughput Nucleotide Sequencing; Humans; Placenta; Pregnancy; Pregnancy Trimester, First; Single-Cell Analysis; Trophoblasts
PubMed: 30402542
DOI: 10.1126/sciadv.aau4788 -
American Journal of Obstetrics and... Feb 2022Physiological transformation with remodeling of the uteroplacental spiral arteries is key to a successful placentation and normal placental function. It is an intricate... (Review)
Review
Physiological transformation with remodeling of the uteroplacental spiral arteries is key to a successful placentation and normal placental function. It is an intricate process that involves, but is not restricted to, complex interactions between maternal decidual immune cells and invasive trophoblasts in the uterine wall. In normal pregnancy, the smooth muscle cells of the arterial tunica media of uteroplacental spiral arteries are replaced by invading trophoblasts and fibrinoid, and the arterial diameter increases 5- to 10-fold. Poor remodeling of the uteroplacental spiral arteries is linked to early-onset preeclampsia and several other major obstetrical syndromes, including fetal growth restriction, placental abruption, and spontaneous preterm premature rupture of membranes. Extravillous endoglandular and endovenous trophoblast invasions have recently been put forth as potential contributors to these syndromes as well. The well-acknowledged disturbed extravillous invasion of maternal spiral arteries in preeclampsia is summarized, as are briefly novel concepts of disturbed extravillous endoglandular and endovenous trophoblast invasions. Acute atherosis is a foam cell lesion of the uteroplacental spiral arteries associated with poor remodeling. It shares some morphologic features with early stages of atherosclerosis, but several molecular differences between these lesions have also recently been revealed. Acute atherosis is most prevalent at the maternal-fetal interface, at the tip of the spiral arteries. The localization of acute atherosis downstream of poorly remodeled arteries suggests that alterations in blood flow may trigger inflammation and foam cell development. Acute atherosis within the decidua basalis is not, however, confined to unremodeled areas of spiral arteries or to hypertensive disorders of pregnancy and may even be present in some clinically uneventful pregnancies. Given that foam cells of atherosclerotic lesions are known to arise from smooth muscle cells or macrophages activated by multiple types of inflammatory stimulation, we have proposed that multiple forms of decidual vascular inflammation may cause acute atherosis, with or without poor remodeling and/or preeclampsia. Furthermore, we propose that acute atherosis may develop at different gestational ages, depending on the type and degree of the inflammatory insult. This review summarizes the current knowledge of spiral artery remodeling defects and acute atherosis in preeclampsia. Some controversies will be presented, including endovascular and interstitial trophoblast invasion depths, the concept of 2-stage trophoblast invasion, and whether the replacement of maternal spiral artery endothelium by fetal endovascular trophoblasts is permanent. We will discuss the role of acute atherosis in the pathophysiology of preeclampsia and short- and long-term health correlates. Finally, we suggest future opportunities for research on this intriguing uteroplacental interface between the mother and fetus.
Topics: Atherosclerosis; Decidua; Female; Humans; Placenta; Placentation; Pre-Eclampsia; Pregnancy; Trophoblasts; Uterine Artery; Vascular Remodeling
PubMed: 32971013
DOI: 10.1016/j.ajog.2020.09.026 -
Cell Reports Jan 2023During human pregnancy, placenta-derived extravillous trophoblasts (EVTs) invade the decidua and communicate with maternal immune cells. The decidua distinguishes into...
During human pregnancy, placenta-derived extravillous trophoblasts (EVTs) invade the decidua and communicate with maternal immune cells. The decidua distinguishes into basalis (decB) and parietalis (decP). The latter remains unaffected by EVT invasion. By defining a specific gating strategy, we report the accumulation of macrophages in decB. We describe a decidua basalis-associated macrophage (decBAM) population with a differential transcriptome and secretome compared with decidua parietalis-associated macrophages (decPAMs). decBAMs are CD11c and efficient inducers of Tregs, proliferate in situ, and secrete high levels of CXCL1, CXCL5, M-CSF, and IL-10. In contrast, decPAMs exert a dendritic cell-like, motile phenotype characterized by induced expression of HLA class II molecules, enhanced phagocytosis, and the ability to activate T cells. Strikingly, EVT-conditioned media convert decPAMs into a decBAM phenotype. These findings assign distinct macrophage phenotypes to decidual areas depending on placentation and further highlight a critical role for EVTs in the induction of decB-associated macrophage polarization.
Topics: Pregnancy; Female; Humans; Pregnancy Trimester, First; Decidua; Trophoblasts; Phenotype; Macrophages
PubMed: 36640334
DOI: 10.1016/j.celrep.2022.111977 -
International Journal of Molecular... Jun 2020Interventions to prevent pregnancy complications have been largely unsuccessful. We suggest this is because the foundation for a healthy pregnancy is laid prior to the... (Review)
Review
Interventions to prevent pregnancy complications have been largely unsuccessful. We suggest this is because the foundation for a healthy pregnancy is laid prior to the establishment of the pregnancy at the time of endometrial decidualization. Humans are one of only a few mammalian viviparous species in which decidualization begins during the latter half of each menstrual cycle and is therefore independent of the conceptus. Failure to adequately prepare (decidualize) the endometrium hormonally, biochemically, and immunologically in anticipation of the approaching blastocyst-including the downregulation of genes involved in the pro- inflammatory response and resisting tissue invasion along with the increased expression of genes that promote angiogenesis, foster immune tolerance, and facilitate tissue invasion-leads to abnormal implantation/placentation and ultimately to adverse pregnancy outcome. We hypothesize, therefore, that the primary driver of pregnancy health is the quality of the soil, not the seed.
Topics: Animals; Autocrine Communication; Biomarkers; Decidua; Embryo Implantation; Endometrium; Female; Gene Expression Regulation; Humans; Paracrine Communication; Placentation; Pregnancy; Pregnancy Complications; Pregnancy Outcome
PubMed: 32521725
DOI: 10.3390/ijms21114092 -
International Journal of Molecular... Mar 2020Reproduction is a fundamental process for the preservation of the human species. This process requires a sequence of orchestrated events that are necessary for a... (Review)
Review
Reproduction is a fundamental process for the preservation of the human species. This process requires a sequence of orchestrated events that are necessary for a successful pregnancy. Two of the most critical steps in the establishment of human pregnancy are implantation and decidualization, which are required for maternal interactions with the developing embryo. This review primarily highlights the physiological aspects of these two events and the adverse pregnancy outcomes from defective implantation and decidualization. The focus of this review is to provide a general concept of the mechanisms involved during the window of implantation, description of components involved in the process and possible pathologies that could disrupt the embryo implantation and decidualization and specifically as it applies to women and non-human primates.
Topics: Abortion, Habitual; Animals; Decidua; Embryo Implantation; Female; Humans; MicroRNAs; Pregnancy; Primates
PubMed: 32183093
DOI: 10.3390/ijms21061973