Establishment of the fetal-maternal interface: developmental events in human implantation and placentation

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: May 17, 2023

Early pregnancy is a complex and well-orchestrated differentiation process that involves all the cellular elements of fetal-maternal interface. Aberrant trophoblast-decidual interactions can lead to miscarriage disorders occur later in pregnancy, including preeclampsia, intrauterine fetal growth restriction, preterm labor. A great deal research on regulation implantation placentation has been performed wide range species. However, there significant species variation regarding trophoblast as well decidual-specific gene expression regulation. Most relevant information obtained from studies using mouse models. comprehensive understanding physiology pathology human only recently because emerging advanced technologies. With derivation stem cells, 3D-organoid cultures, single-cell analyses differentiated cell type-specific transcript profiles functions were generated, each exhibited unique signature. Additionally, through integrative transcriptomic information, researchers uncover dysfunction embryonic placental cells peri-implantation embryos early pathological placenta. In fact, clinical utility trafficking applied for noninvasive prenatal diagnosis aneuploidies prediction complications. Furthermore, recent have proposed viable path toward development therapeutic strategies targeting placenta-enriched molecules diseases.

Language: Английский

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Effects of polycyclic aromatic hydrocarbons (PAHs) on pregnancy, placenta, and placental trophoblasts

Ecotoxicology and Environmental Safety, Journal Year: 2023, Volume and Issue: 262, P. 115314 - 115314

Published: Aug. 2, 2023

Polycyclic aromatic hydrocarbons (PAHs) are a group of persistent organic pollutants that carcinogenic, mutagenic, endocrine-toxic, and immunotoxic. PAHs can be found in maternal fetal blood the placenta during pregnancy. They may thus affect placental development. Therefore, exposure levels toxic effects deserve further study discussion. This review aims to summarize current knowledge on their metabolites pregnancy birth outcomes trophoblast cells. A growing number epidemiological studies detected PAH-DNA adducts as well 16 high-priority human showed PAH is associated with adverse outcomes. Trophoblasts important cells involved development function. In vitro have shown either mixtures, benzo(a)pyrene (BaP) or BaP metabolite benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) affected cell viability, differentiation, migration, invasion through various signaling pathways. Furthermore, similar BPDE could also observed BaP-treated mouse models were related miscarriage. Although data show outcomes, (population studies, animal studies) necessary specific different trophoblasts

Language: Английский

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Single-nuclei RNA sequencing (snRNA-seq) uncovers trophoblast cell types and lineages in the mature bovine placenta

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(12)

Published: March 13, 2023

Ruminants have a semi-invasive placenta, which possess highly vascularized placentomes formed by maternal endometrial caruncles and fetal placental cotyledons required for development to term. The synepitheliochorial placenta of cattle contains at least two trophoblast cell populations, including uninucleate (UNC) binucleate (BNC) cells that are most abundant in the cotyledonary chorion placentomes. interplacentomal is more epitheliochorial nature with developing specialized areolae over openings uterine glands. Of note, types cellular molecular mechanisms governing differentiation function little understood ruminants. To fill this knowledge gap, intercotyledonary areas mature day 195 bovine were analyzed single nuclei analysis. Single-nuclei RNA-seq analysis found substantial differences type composition transcriptional profiles between distinct regions placenta. Based on clustering marker gene expression, five different identified chorion, proliferating differentiating UNC BNC cotyledon. Cell trajectory analyses provided framework understanding into BNC. upstream transcription factor binding differentially expressed genes candidate set regulator factors regulating differentiation. This foundational information useful discover essential biological pathways underpinning

Language: Английский

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A comprehensive human embryo reference tool using single-cell RNA-sequencing data

Nature Methods, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 14, 2024

Stem cell-based embryo models offer unprecedented experimental tools for studying early human development. The usefulness of hinges on their molecular, cellular and structural fidelities to in vivo counterparts. To authenticate models, single-cell RNA sequencing has been utilized unbiased transcriptional profiling. However, an organized integrated RNA-sequencing dataset, serving as a universal reference benchmarking remains unavailable. Here we developed such through the integration six published datasets covering development from zygote gastrula. Lineage annotations are contrasted validated with available nonhuman primate datasets. Using stabilized Uniform Manifold Approximation Projection, constructed embryogenesis prediction tool, where query can be projected annotated predicted cell identities. this examined highlighting risk misannotation when relevant references not authentication.

Language: Английский

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Why study human embryo development?

Developmental Biology, Journal Year: 2024, Volume and Issue: 509, P. 43 - 50

Published: Feb. 5, 2024

Understanding the processes and mechanisms underlying early human embryo development has become an increasingly active important area of research. It potential for insights into clinical issues such as pregnancy loss, origins congenital anomalies developmental adult disease, well fundamental biology. Improved culture systems preimplantation embryos, combined with new tools single cell genomics live imaging, are providing similarities differences between mouse development. However, access to material is still restricted extended embryos regulatory ethical concerns. Stem cell-derived models different phases can potentially overcome these limitations provide a scalable source explore postimplantation stages To date, clearly incomplete replicas normal but future technological improvements be envisaged. The environment studies remains fully resolved.

Language: Английский

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TGFβ signalling: a nexus between inflammation, placental health and preeclampsia throughout pregnancy

Human Reproduction Update, Journal Year: 2024, Volume and Issue: 30(4), P. 442 - 471

Published: March 22, 2024

Abstract BACKGROUND The placenta is a unique and pivotal organ in reproduction, controlling crucial growth cell differentiation processes that ensure successful pregnancy. Placental development tightly regulated dynamic process, which the transforming factor beta (TGFβ) superfamily plays central role. This family of pleiotropic factors heavily involved regulating various aspects reproductive biology, particularly trophoblast during first trimester TGFβ signalling precisely regulates invasion transition from cytotrophoblasts to extravillous trophoblasts, an epithelial-to-mesenchymal transition-like process. Later pregnancy, ensures proper vascularization angiogenesis placental endothelial cells. Beyond its role trophoblasts cells, contributes polarization function decidual macrophages by promoting maternal tolerance semi-allogeneic foetus. Disturbances early have been associated with several pregnancy complications, including preeclampsia (PE) one severe complications. Emerging evidence suggests pathogenesis PE, thereby offering potential target for intervention human placenta. OBJECTIVE AND RATIONALE comprehensive review aims explore elucidate roles major members superfamily, TGFβs, bone morphogenetic proteins (BMPs), activins, inhibins, nodals, (GDFs), context function. focusses on their interactions within types placenta, namely immune both normal pregnancies complicated PE throughout SEARCH METHODS A literature search was carried out using PubMed Google Scholar, searching terms: ‘TGF preeclampsia’, ‘pregnancy TGF signalling’, ‘preeclampsia tgfβ’, bmp’, gdf’, activin’, ‘endoglin pregnancy’, ‘tgfβ ‘bmp ‘gdf ‘activin ‘Hofbauer tgfβ ‘placental ‘endothelial cells ‘endothelium ‘trophoblast Smad’, development’, ‘TGFβ function’, dysfunction ‘vascular remodelling TGFβ’, ‘inflammation ‘immune response NK cells’, tregs’, ‘NK ‘Tregs preeclampsia’. Only articles published English until 2023 were used. OUTCOMES understanding interconnected functions main provides valuable insights into essential foetus By orchestrating invasion, vascularization, tolerance, tissue remodelling, ligands contribute functioning healthy maternal–foetal interface. However, dysregulation has implicated where shallow defective vascular decreased uteroplacental perfusion, observed are all affected altered signalling. WIDER IMPLICATIONS important implications research clinical practice. Further investigation required understand underlying mechanisms, different regulation under pathophysiological conditions, order discover new therapeutic targets. Distinguishing between clinically manifested subtypes studying holistically step. To put this knowledge practice, pre-clinical animal models combined technologies needed. may also lead improved identify targets, ultimately improving outcomes reducing burden PE.

Language: Английский

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Organoids in Haematologic Research: Advances and Future Directions

Cell Proliferation, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 26, 2025

ABSTRACT Organoid technology, as a revolutionary biomedical tool, has shown immense potential in haematological research recent years. By using three‐dimensional (3D) cell culture systems constructed from pluripotent stem cells (PSCs) or adult (ASCs), organoids can highly mimic the characteristics of vivo organs, thereby offering significant for investigating human organ development, disease processes and treatment strategies. This review introduces development focuses on their progress research, including haematopoietic‐related organoids, immune‐related used studying blood system diseases. It discusses prospects, challenges future outlook field haematology. aims to provide latest advancements directions organoid technology references insights into further exploration this field.

Language: Английский

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Chromosomal instability in human trophoblast stem cells and placentas

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 25, 2025

The human placenta, a unique tumor-like organ, is thought to exhibit rare aneuploidy associated with adverse pregnancy outcomes. Discrepancies in reported prevalence placentas stem from limitations modeling and detection methods. Here, we use isogenic trophoblast cells (TSCs) derived both naïve primed pluripotent (hPSCs) reveal the spontaneous occurrence of aneuploidy, suggesting chromosomal instability (CIN) as an inherent feature lineage. We identify potential pathways contributing tolerance CIN, such autophagy, which may support survival aneuploid cells. Despite extensive abnormalities, TSCs maintain their proliferative differentiation capacities. These findings are further validated placentas, where observe high heterogeneous across trophoblasts, particularly invasive extravillous trophoblasts. Our study challenges traditional view placenta provides insights into implications CIN placental function.

Language: Английский

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A placental model of SARS-CoV-2 infection reveals ACE2-dependent susceptibility and differentiation impairment in syncytiotrophoblasts

Nature Cell Biology, Journal Year: 2023, Volume and Issue: 25(8), P. 1223 - 1234

Published: July 13, 2023

Abstract SARS-CoV-2 infection causes COVID-19. Several clinical reports have linked COVID-19 during pregnancy to negative birth outcomes and placentitis. However, the pathophysiological mechanisms underpinning placentation early are not clear. Here, shed light on this, we used induced trophoblast stem cells generate an in vitro placenta model. We identified that syncytiotrophoblasts could be infected through angiotensin-converting enzyme 2 (ACE2). Using a co-culture model of vertical transmission, confirmed ability virus infect previous endometrial cell infection. further demonstrated transcriptional changes led impairment cellular processes, reduced secretion HCG hormone morphological vital for syncytiotrophoblast function. Furthermore, different antibody strategies antiviral drugs restore these impairments. In summary, established scalable tractable platform study placental types highlighted its use studying protect placenta.

Language: Английский

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Zika virus targets human trophoblast stem cells and prevents syncytialization in placental trophoblast organoids

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Sept. 8, 2023

Zika virus (ZIKV) infection during pregnancy threatens and fetal health. However, the infectivity pathological effects of ZIKV on placental trophoblast progenitor cells in early human embryos remain largely unknown. Here, using stem (hTSCs), we demonstrated that hTSCs were permissive to infection, resistance increased with hTSC differentiation. Combining gene knockout transcriptome analysis, intrinsic expression AXL TIM-1, absence potent interferon (IFN)-stimulated genes (ISGs) IFNs contributed high sensitivity ZIKV. Furthermore, our newly developed hTSC-derived organoid (hTSC-organoid), disrupted structure mature hTSC-organoids inhibited syncytialization. Single-cell RNA sequencing (scRNA-seq) further stemness proliferation cytotrophoblast (CTBs) probably led a preeclampsia (PE) phenotype. Overall, results clearly demonstrate represent major target ZIKV, reduced syncytialization may result from developing placenta. These findings deepen understanding characteristics consequences embryos.

Language: Английский

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