Progestogen-driven B7-H4 contributes to onco-fetal immune tolerance

Cell, Journal Year: 2024, Volume and Issue: 187(17), P. 4713 - 4732.e19

Published: July 4, 2024

Immune tolerance mechanisms are shared in cancer and pregnancy. Through cross-analyzing single-cell RNA-sequencing data from multiple human types the maternal-fetal interface, we found B7-H4 (VTCN1) is an onco-fetal immune checkpoint. We showed that genetic deficiency of resulted activation fetal resorption allogeneic pregnancy models. Analogously, contributed to MPA/DMBA-induced breast progression, accompanied by CD8

Language: Английский

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Maternal–Fetal Compatibility in Recurrent Pregnancy Loss

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(8), P. 2379 - 2379

Published: April 19, 2024

Nowadays, recurrent pregnancy loss (RPL) is an undesirable condition suffered by many patients of reproductive age. In this scenario, certain immune cell populations and molecules, involved in maternal–fetal compatibility, have emerged as factors related with the pathogenesis RPL. Among them, uterine Natural Killer cells (uNKs) appear to be great relevance. These are numerous processes during pregnancy, such remodeling spiral arteries or control trophoblast invasion. functions regulated interactions that these establish extravillous trophoblast, mainly through their Immunoglobulin-like Receptors (KIRs) Human Leukocyte Antigen-C (HLA-C) molecules expressed embryo. A high level polymorphism has been reported for both interaction, some possible KIR–HLA-C combinations being associated increased risk However, complexity interface goes beyond this, other HLA also pathology. review, we will discuss role uNKs well polymorphisms clinical implications binding. We address involvement other, different RPL, current advice on appropriate management ‘immunological mismatch’, thus covering main aspects regarding compatibility

Language: Английский

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Role of immune cells in the establishment of implantation and maintenance of pregnancy and immunomodulatory therapies for patients with repeated implantation failure and recurrent pregnancy loss

Reproductive Medicine and Biology, Journal Year: 2024, Volume and Issue: 23(1)

Published: Jan. 1, 2024

Abstract Background Immune cells play an important role in the establishment of pregnancy, and abnormalities immune system can cause implantation failure miscarriage. Methods Previous papers have been summarized reproduction is reviewed. Results The environment uterus changes drastically from before to after pregnancy maintain pregnancy. In allogeneic pregnancies, immature dendritic (DCs) that induce tolerance outside flow into uterus, mature DCs remain express programmed cell death ligand 2, which suppresses response. Macrophages are classified M1‐macrophages, inflammation, M2‐macrophages, suppress inflammation; M1‐macrophages required for luteinization, M2‐macrophages differentiation endometrial epithelial enable implantation. Regulatory T cells, rejection, essential maintenance pregnancies. Implantation fetal loss associated with decreased numbers or qualitative DCs, macrophages, regulatory cells. clinical usefulness immunomodulatory therapies patients repeated recurrent has reported. Conclusion provision individualized medical care cases miscarriage may improve outcomes.

Language: Английский

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Early human development and stem cell-based human embryo models

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(10), P. 1398 - 1418

Published: Oct. 1, 2024

Language: Английский

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Comparative analysis of the syncytiotrophoblast in placenta tissue and trophoblast organoids using snRNA sequencing

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 4, 2024

Abstract The outer surface of chorionic villi in the human placenta consists a single multinucleated cell called syncytiotrophoblast (STB). unique cellular ultrastructure STB presents challenges deciphering its gene expression signature at single-cell level, as contains billions nuclei cell. There are many gaps understanding molecular mechanisms and developmental trajectories involved formation differentiation. To identify underlying control STB, we performed comparative nucleus (SN) (SC) RNA sequencing on placental tissue tissue-derived trophoblast organoids (TOs). We found that SN was essential to capture population from both TOs. Differential pseudotime analysis TO-derived identified three distinct nuclear subtypes reminiscent those recently vivo . These included juvenile exhibited CTB marker expression, enriched genes oxygen sensing, finally subtype transport GTPase signaling molecules. Notably, suspension culture conditions TOs restore native orientation (STB out ) showed elevated canonical markers pregnancy hormones, along with greater proportion specializing signaling, compared cultivated an inverted polarity ). Gene regulatory novel differentiation conserved TOs, including chromatin remodeler RYBP, STB-specific protein expression. CRISPR/Cas9 knockout RYBP did not impact cell-cell fusion; however, bulk revealed downregulation hormone CSH1 upregulation multiple associated oxygen-sensing subtype. Finally, signatures amongst first trimester tissue, full-term identifying commonalities but also notable variability across each sample type. This indicates is responsive environmental context. Our findings emphasize utility accurately model observed , offering versatile platform for unraveling governing functions biology disease.

Language: Английский

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Assessing the impact and risk of immunomodulatory compounds on pregnancy

Journal of Reproductive Immunology, Journal Year: 2025, Volume and Issue: 169, P. 104453 - 104453

Published: Feb. 16, 2025

There have been remarkable advancements in understanding the complex and dynamic immune biological processes engaged during all stages of pregnancy. Exquisite control is critical to successful outcome pregnancy from ovulation birth. are many immunomodulatory therapeutics that may offer beneficial treatment options for a variety diseases (e.g., inflammation/autoimmunity, cancer) patients or desire become pregnant. It important understand potential these alter inform clinical risk relative The Health Environmental Sciences Institute-Developmental Reproductive Toxicology/Immuno-safety Technical Committee (HESI DART/ITC) conducted survey on approaches assess adverse outcomes with immunomodulators. HESI DART/ITC also organized workshop an extended discussion mechanisms pregnancy, adequacy current tools/methodologies identify concerns hazards therapies, ways address scientific gaps, global regulatory considerations across various modalities indications. In this manuscript we summarize learnings efforts characterize within patient population, promote more informed decisions, enable safer pharmacological interventions

Language: Английский

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IGF2BP1 Enhances Neprilysin mRNA Stability to Promote Proliferation, Invasion, and Angiogenesis in Placental Trophoblasts

International Journal of General Medicine, Journal Year: 2025, Volume and Issue: Volume 18, P. 967 - 980

Published: Feb. 1, 2025

Preeclampsia (PE) is a severe gestational disorder characterized by sudden hypertension and proteinuria, with substantial risks to both mother fetus. This study aims delineate the role of neprilysin, metalloprotease known for its in modulating vasoactive peptides, pathophysiology PE. We recruited cohort 57 participants, comprising 38 patients diagnosed PE 19 healthy controls, matched demographic clinical characteristics. Neprilysin expression was assessed serum placental tissues through quantitative RT-qPCR Western blot analyses. Functional impacts neprilysin modulation were explored via siRNA knockdown overexpression HTR8/SVneo cells, followed assessments oxidative stress, mitochondrial function, apoptosis, trophoblast invasion using various biochemical assays including CCK-8, DCFH-DA, JC-1 staining, flow cytometry. Our results demonstrate marked compared controls. Elevated levels positively correlated increased systolic diastolic blood pressures. In functional assays, alleviated H2O2-induced restored improved cell migration EVT cells. Conversely, IGF2BP1, regulator mRNA stability, exacerbated intensified cellular damage under stress conditions. The reciprocal regulation IGF2BP1 highlights critical molecular interplay impacting resilience These findings establish as mediator pathogenesis PE, where aberrant linked hypertensive symptoms impaired function. interaction between provides potential therapeutic target mitigating progression suggesting avenues future intervention strategies.

Language: Английский

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Adverse maternal and fetal outcomes in mouse models of prenatal infections

Wellcome Open Research, Journal Year: 2025, Volume and Issue: 10, P. 142 - 142

Published: March 18, 2025

Background Prenatal infections are a leading cause of adverse pregnancy outcomes, yet the mechanisms underlying pathogen-specific effects on maternal and fetal health remain poorly understood. Methods Here we conducted comparative analysis four mouse models prenatal infection: Toxoplasma gondii (intraperitoneal), vaccinia virus (intranasal), murine cytomegalovirus (intravenous) influenza A (intranasal). Results We found markedly different morbidity mortality, with T. causing severe pregnancy-specific pathology to mortality by 8 days post-infection, despite similar pathogen loads in pregnant non-pregnant mice. Vaccinia caused morbidity, while induced only mild, transient effects. The T.gondii infection was most likely due immunopathology, possibly tissue infection. None pathogens directly infected fetuses, both significantly impaired uterine vascular remodelling growth. Notably, be modifier local but not systemic immune responses, reduced inflammatory cytokine production mice compared controls. Conclusions These provide systematic platform for understanding complications identifying therapeutic targets.

Language: Английский

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Immunology of Recurrent Pregnancy Loss Update

Current Obstetrics and Gynecology Reports, Journal Year: 2025, Volume and Issue: 14(1)

Published: March 22, 2025

Language: Английский

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Uteroplacental microvascular remodeling in health and disease

Acta Physiologica, Journal Year: 2025, Volume and Issue: 241(5)

Published: March 29, 2025

The microvascular system is essential for delivering oxygen and nutrients to tissues while removing metabolic waste. During pregnancy, the uteroplacental undergoes extensive remodeling meet increased demands of fetus. Key adaptations include vessel dilation increases in vascular volume, density, permeability, all which ensure adequate placental perfusion maintaining stable maternal blood pressure. Structural functional abnormalities microvasculature are associated with various gestational complications, posing both immediate long-term risks health mother infant. In this review, we describe changes microvessels during discuss pathogenic mechanisms underlying diseases such as preeclampsia, fetal growth restriction, diabetes, summarize current clinical research approaches monitoring health. We also provide an update on models complications explore solutions several unresolved challenges. With advancements techniques, anticipate significant progress understanding managing these diseases, ultimately leading new therapeutic strategies improve

Language: Английский

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