Biology and Pathophysiology of Placenta Accreta Spectrum Disorder

Obstetrics and Gynecology, Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

Placenta accreta spectrum (PAS) disorders present a significant clinical challenge, characterized by abnormal placental adherence to the uterine wall secondary scarring. With rising global cesarean delivery rates, incidence of this iatrogenic disorder has increased, underscoring critical need for an understanding its pathophysiology inform management and prevention strategies. Normal placentation depends on tightly regulated extravillous trophoblast invasion into decidua, spiral artery remodeling, interactions with extracellular matrix, immune modulation. Uterine scarring disrupts balance, creating environment deficient in key regulatory signals required coordinated implantation decidualization. In PAS, loss inhibitory decidual cues boundary limits permits unrestrained environment. Dysregulated signaling, along inflammatory milieu scarred tissues, exacerbates development. Current prenatal imaging focuses appearance excessive fibrinoid deposition, matrix incomplete transformation as surrogates PAS risk stratification. Emerging single-cell RNA sequencing proteomic profiling offer insights biomarkers pathways that enable targeted interventions. Preventive efforts should prioritize reducing rates limit Advances regenerative medicine bioengineering, including matrix–modulating biomaterials, growth factor therapies, antifibrotic interventions, hold promise improving scar healing risk. This review bridges foundational science application, emphasizing importance underlying biology make difference detecting, treating, preventing PAS. Addressing drivers is maternal neonatal outcomes increasingly prevalent condition.

Language: Английский

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The multifaceted roles of the transcriptional coactivator TAZ in extravillous trophoblast development of the human placenta

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(16)

Published: April 14, 2025

Insights into the molecular processes that drive early development of human placenta is crucial for our understanding pregnancy complications such as preeclampsia and fetal growth restriction, since defects in maturation its epithelial cell, trophoblast, have been detected severe forms these diseases. However, key regulators specifying differentiated trophoblast subtypes are only slowly emerging. By using diverse cell models, we herein show transcriptional coactivator HIPPO signaling, TAZ, plays a pivotal role invasive extravillous trophoblasts (EVTs), cells essential decidual vessel remodeling adaption maternal blood flow to placenta. Ribonucleic acid sequencing (RNA-seq) or protein analyses upon TAZ gene silencing CRISPR-Cas9-mediated knockout differentiating stem cells, organoids, primary EVTs, choriocarcinoma villous explant cultures unraveled promoted expression genes associated with EVT identity, motility, survival. Accordingly, depletion chemical inhibition interacting TEA domain family member 1 (TEAD1), impaired differentiation, invasion, migration triggered apoptosis different models. Notably, also suppressed cycle self-renewal prevented EVTs from fusion organoids cultures. Moreover, leukocyte antigen G (HLA-G) surface increased NUAK1 kinase thereby maintaining own expression. In summary, multifaceted lineage by controlling biological initiate preserve differentiation.

Language: Английский

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Comparative analysis of rhesus macaque and human placental organoids highlights evolutionary differences in placentation

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

Published: Oct. 12, 2024

Abstract Throughout evolution, the placenta has diversified in both structure and cellular composition while maintaining its fundamental function. Trophoblasts are fetal-derived cells responsible for nourishing protecting developing fetus a universal component of all placentas. While primate placentas exhibit many shared morphological features, species-specific differences gene expression remain largely unexplored, primarily due to lack suitable vitro models. To address this gap, we developed organoids from rhesus macaque placentas, including trophoblast maternal-derived decidua types, compared them with derived human We performed comparative single-cell RNA sequencing delineate distinct transcriptional signatures between trophoblasts. further defined differentiation trajectories leading multinucleated syncytiotrophoblast, highlighting unique This work establishes novel models non-human characterizes profiles macaques humans, providing insights into interspecies variations placental biology.

Language: Английский

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Exploring the black box of human reproduction: endometrial organoids and assembloids - generation, implantation modeling, and future clinical perspectives

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Oct. 23, 2024

One of the critical processes in human reproduction that is still poorly understood implantation. The implantation an early embryo considered a significant limitation successful pregnancy. Therefore, researchers are trying to develop ideal model endometrium vitro can mimic endometrial micro-environment vivo as much possible. ultimate goal modeling study molecular interactions at embryo-maternal interface and use this diagnostic tool for infertility. Significant progress has been made over years generating such models. first experiments involved animal models, which undoubtedly valuable, but same time, their dissimilarities with tissue represent obstacle further research. This fact led basic monolayer coculture systems using uterine cells obtained from biopsies and, later on, complex multilayer With engineering methods various cultivation systems, it possible form two-dimensional (2D) models three-dimensional (3D) organoids novel assembloids recapitulate many aspects architecture cell composition. These have already helped provide new insight into embryo-endometrium interplay. main aim paper comprehensive review past current approaches generation, feasibility, potential clinical application infertility treatment.

Language: Английский

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

Published: Nov. 1, 2024

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, fully differentiated subtype. Notably, suspension culture conditions TOs restore native orientation (STB out ) showed elevated canonical markers pregnancy hormones, along with greater proportion terminally mature subtype, compared cultivated an inverted polarity ). Gene regulatory novel differentiation conserved TOs, including chromatin remodeler RYBP, STB-specific protein expression. 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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Cytokine modulation and immunoregulation of uterine NK cells in pregnancy disorders

Cytokine & Growth Factor Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

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Early spiral arteriole remodeling in the uterine–placental interface: A rat model

Journal of Anatomy, Journal Year: 2024, Volume and Issue: 244(6), P. 1054 - 1066

Published: Jan. 30, 2024

Abstract The mammalian placenta's interface with the parent is a richly vascularized tissue whose development relies upon communication between many different cell types within uterine microenvironment. blood vessels of are reshaped during pregnancy into wide‐bore, flaccid that convey parental to exchange region placenta. Invasive trophoblast as well macrophages and Natural Killer cells involved in stepwise remodeling these their respective contributions this crucial process still being delineated. However, earliest steps arteriole understudied they difficult study humans, other species lack deep invasion so prominent feature placentation humans. Here, we further characterize rat, hemochorial akin model system which tease apart earliest, relatively events spiral remodeling. We show rat uterine−placental increases size vascularity rapidly, before invasion. stages arterioles uterine–placental follow sequence anatomical changes similar those there arterioles' muscular tunica media prior marked influx immune cells. tractable better understand cell/cell interactions occurring vivo an intact microenvironment over time.

Language: Английский

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Single-cell transcriptomic analysis of immune cell dynamics in the healthy human endometrium

Biochemistry and Biophysics Reports, Journal Year: 2024, Volume and Issue: 39, P. 101802 - 101802

Published: July 26, 2024

The microenvironment of the endometrial immune system is crucial to success placental implantation and healthy pregnancy. However, functionalities cells across various stages reproductive cycle have yet be fully comprehended. To address this, we conducted advanced bioinformatic analysis on 230,049 high-quality single-cell transcriptomes from samples obtained during proliferative, secretory, early pregnancy, late pregnancy stages. Our investigation has unveiled that proliferative natural killer (NK) cells, a potential source NK exhibit most robust differentiation non-pregnant We also identified similar trajectories originating four Notably, demonstrate highest oxidative phosphorylation metabolism activity, and, in conjunction with macrophages T strongest type II interferon response. With spatial transcriptome data, discerned immune-non-immune interactions are associated promotion inhibition cell proliferation, migration Furthermore, compiled lists stage-specific risk genes implicated diseases, which hold promise as disease biomarkers. study provides insights into dynamics different stages, thus serving reference for detecting pathological changes

Language: Английский

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Placental Origins of Preeclampsia: Insights from Multi-Omic Studies

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9343 - 9343

Published: Aug. 28, 2024

Preeclampsia (PE) is a major cause of maternal and neonatal morbidity mortality worldwide, with the placenta playing central role in disease pathophysiology. This review synthesizes recent advancements understanding molecular mechanisms underlying PE, focusing on placental genes, proteins, genetic variants identified through multi-omic approaches. Transcriptomic studies bulk tissue have many dysregulated genes PE placenta, including signature gene, Fms-like tyrosine kinase 1 (

Language: Английский

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The ENDOMIX perspective: how everyday chemical mixtures impact human health and reproduction by targeting the immune system

Biology of Reproduction, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 24, 2024

Abstract Endocrine-disrupting chemicals are natural and synthetic compounds found ubiquitously in the environment that interfere with hormonal-immune axis, potentially impacting human health reproduction. Exposure to endocrine-disrupting has been associated numerous risks, such as neurodevelopmental disorders, metabolic syndrome, thyroid dysfunction, infertility, cancers. Nevertheless, current approach establishing causality between these substances disease outcomes limitations. Epidemiological experimental research on faces challenges accurately assessing chemical exposure interpreting non-monotonic dose response curves. In addition, most studies have focused single or simple mixtures, overlooking complex real-life exposures mechanistic insights, particular regarding chemicals' impact immune system. The ENDOMIX project, funded by EU’s Horizon Health Program, addresses integrating epidemiological, risk assessment, immunotoxicology methodologies. This systemic comprises triangulation of cohort, vitro, vivo data determine combined effects mixtures. present review presents discusses literature reproduction context immunotolerance disruption mode action. It further underscores perspective elucidate immune-reproductive health.

Language: Английский

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