M2 macrophages dampenin uterosterile inflammation to prevent preterm birth and improve neonatal outcomes DOI Creative Commons
Valeria Garcia‐Flores, Zhenjie Liu, Roberto Romero

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: July 19, 2023

SUMMARY Preterm birth (PTB), often preceded by preterm labor, is a major cause of neonatal morbidity and mortality worldwide. Most PTB cases involve intra-amniotic inflammation without detectable microorganisms, termed in utero sterile inflammation, for which there no established treatment. Here, we propose homeostatic macrophages to prevent adverse outcomes caused inflammation. Single-cell atlases the maternal-fetal interface revealed that maternal are reduced with human labor. M2 macrophage treatment prevented mice Specifically, halted premature labor suppressing inflammatory responses amniotic cavity, including inflammasome activation, mitigated placental offspring lung Moreover, restored gut homeostasis enhanced resistance systemic bacterial infection. Our findings show promising strategy mitigate improve from

Language: Английский

The landscape of decidual immune cells at the maternal–fetal interface in parturition and preterm birth DOI Creative Commons
Mu Lv,

Yuanhui Jia,

Jiaqi Dong

et al.

Inflammation Research, Journal Year: 2025, Volume and Issue: 74(1)

Published: March 4, 2025

Parturition is similar to an inflammatory response in which resident and infiltrating immune cells release cytokines chemokines into the maternal-fetal interface, promoting expulsion of fetus from mother. The untimely activation these pathways can result preterm labor. interface composed mainly decidual tissue placental villous space. objective this review examine role mechanisms during parturition birth. A deeper understanding at could provide significant insight birth pathogenesis. We searched major databases (including PubMed, Web Science, Google Scholar etc.) for literature encompassing cells, up July 2024 combined with studies found reference lists included studies. Decidual neutrophils mediators that facilitate parturition. M1/M2 ratio macrophages increases among population. Mast may cause uterine contractions. In birth, there increase CD56dimCD16+ natural killer immature dendritic cells. Th1/Th2 Th17/Treg leads Women had a higher proportion B ILC2 help protect steady-state environment interface. invariant NKT plays important inflammation-induced These communicate each other. development sequencing technology enables more in-depth study dynamic balance microenvironment crucial maintaining human pregnancy initiation delivery. deep mechanism dysfunction pathogenesis

Language: Английский

Citations

2

Immune Treatment Strategies in Unexplained Recurrent Pregnancy Loss DOI

Cai Rui,

Qinbo Yang,

Yingjun Liao

et al.

American Journal of Reproductive Immunology, Journal Year: 2025, Volume and Issue: 93(2)

Published: Feb. 1, 2025

ABSTRACT Recurrent pregnancy loss (RPL) is characterized by the occurrence of two or more consecutive losses. Approximately half these cases lack a clear etiology and are termed unexplained recurrent (URPL). Maternal–fetal immune dysfunction thought to be involved in causing URPL. Increased human leukocyte antigen compatibility, susceptibility genes, blocking antibodies, cells can all disrupt tolerance environment maternal–fetal interface. To correct imbalances, some immunotherapies were recently tried used for patients with This review summarizes characteristics mechanisms microenvironment at interface URPL patients, present serve as reference future research.

Language: Английский

Citations

1

Biology and Pathophysiology of Placenta Accreta Spectrum Disorder DOI
Yalda Afshar, Lior Kashani Ligumsky, Helena C. Bartels

et al.

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

Citations

1

Single-cell RNA sequencing of estrual mice reveals PM2.5-induced uterine cell heterogeneity and reproductive toxicity DOI Creative Commons
Shuyin Duan, Yong‐Fei Zheng, Jiaqi Tian

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 284, P. 116968 - 116968

Published: Sept. 4, 2024

Language: Английский

Citations

5

B cells: roles in physiology and pathology of pregnancy DOI Creative Commons

Jinchuan Liu,

Qunxiong Zeng,

Yong‐Gang Duan

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 7, 2024

B cells constitute a diverse and adaptable immune cell population with functions that can vary according to the environment circumstances. The involvement of in pregnancy, as well associated molecular pathways, has yet be investigated. This review consolidates current knowledge on activities regulation during particular focus roles various subsets effects cell-derived factors pregnancy outcomes. Moreover, examines significance cell-associated autoantibodies, cytokines, signaling pathways relation complications such loss, preeclampsia, preterm birth.

Language: Английский

Citations

5

Multi‐organ transcriptomic atlas reveals hallmarks of labour DOI Creative Commons
Duan Ni, Ralph Nanan

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(2)

Published: Feb. 1, 2025

Language: Английский

Citations

0

The single-cell immune profile throughout gestation and its potential value for identifying women at risk for spontaneous preterm birth DOI Creative Commons
Dorien Feyaerts,

Maïgane Diop,

José Galaz

et al.

European Journal of Obstetrics & Gynecology and Reproductive Biology X, Journal Year: 2025, Volume and Issue: 25, P. 100371 - 100371

Published: Feb. 6, 2025

Precisely timed immune adaptations, observed in the maternal circulation, underpin notion of an clock human pregnancy that supports its successful progression and completion at delivery. This is divided into three immunological phases, with first phase starting time conception implantation, shifting second homeostasis tolerance throughout pregnancy, culminating last labor parturition. Disruptions this are reported complications such as spontaneous preterm birth. However, our understanding preceding birth remains scattered. In review, we describe chronology cell adaptations during healthy pregnancies highlight disruption With a focus on single-cell cytometric, proteomic transcriptomic approaches, review recent studies term discuss need for future prospective aimed tracking longitudinally multi-omic scale. Such will be critical determining whether progress accelerated pace or follow preterm-intrinsic pattern when compared to those delivered term.

Language: Английский

Citations

0

Decidual stromal cells: fibroblasts specialized in immunoregulation during pregnancy DOI
Tatiana Llorca, María José Ruiz-Magaña,

Ana C Abadía

et al.

Trends in Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0

The pentameric complex is not required for congenital CMV transmission in seronegative rhesus macaques DOI Open Access
Hsuan-Yuan Wang,

Husam Taher,

Craig N. Kreklywich

et al.

Science Translational Medicine, Journal Year: 2025, Volume and Issue: 17(789)

Published: March 12, 2025

Congenital cytomegalovirus (cCMV) is the leading infectious cause of neonatal neurological impairment worldwide, but viral factors enabling vertical spread across placenta remain undetermined. The pentameric complex (PC), composed subunits gH/gL/UL128/UL130/UL131A, has been demonstrated to be important for entry into nonfibroblast cells in vitro. These findings link PC broad cell tropism and virus dissemination vivo, denoting all as potential targets intervention strategies vaccine development. To determine relevance congenital transmission a translational nonhuman primate model, we engineered rhesus CMV (RhCMV) mutant lacking orthologs UL128 UL130, which diminished infection epithelial However, intravenous inoculation either CD4 + T cell–depleted or immunocompetent RhCMV-seronegative pregnant macaques (RMs) early second trimester with PC-deficient resulted maternal RhCMV peak plasma viremia similar inoculations PC-intact RhCMV, although shedding saliva urine was limited. Infections induced IgG responses that neutralized tissue culture. were reduced, not absent, from animals infected virus, also against gH. Moreover, confirmed multiple by detecting DNA amniotic fluid, indicating transplacental RMs contingent on PC.

Language: Английский

Citations

0

Single-nucleus transcriptional profiling of the placenta reveals the syncytiotrophoblast stress response to COVID-19 DOI Creative Commons
Rachel A. Keuls, Scott A. Ochsner, Mary B. O’Neill

et al.

American Journal of Obstetrics and Gynecology, Journal Year: 2025, Volume and Issue: 232(4), P. S160 - S175.e7

Published: April 1, 2025

COVID-19 in pregnancy is associated with placental immune activation, inflammation, and vascular malperfusion, but its impact on syncytiotrophoblast biology function unclear. This study aimed to determine the effects of maternal syncytiotrophoblasts using single-nucleus transcriptional profiling compare stress responses preeclampsia. For characterization syncytiotrophoblasts, we used RNA sequencing platform, single-cell combinatorial indexing (sci-RNA-seq3), profile villi fetal membranes from unvaccinated patients symptomatic at birth (n = 4), gestational age-matched controls a case critical second trimester delivery term 1). Clustering nuclei differential gene expression analysis was performed Seurat. Gene ontology conducted Enrichr. High-confidence target identify key transcription factor nodes governing response SARS-CoV-2 infection. Bioinformatic approaches were further dataset published preeclampsia signatures. Tissue analysis, including immunofluorescence, validate data histology for an expanded cohort placentas: 6), asymptomatic 3), 5), severe features 7). The analyzed comprised 15 cell clusters 47,889 nuclei. We identified 3 representing fusing mature overlapping distinct COVID-19. analyses indicated that following alterations syncytiotrophoblasts: (1) endoplasmic reticulum activation signaling pathways, unfolded protein integrated response; (2) regulation by CCAAT/enhancer-binding beta (CEBPB), master lineage; (3) upregulation preeclampsia-associated genes. Using complementary methods, confirmed increased levels proteins (eg, BiP, G3BP1) (spliced XBP1 mRNA), CEBPB (phosphorylation) Increased cytotrophoblast proliferation (Ki-67) also detected COVID-19, consistent trophoblast injury. Markers demonstrated similarities phenotype Maternal lineage factor, CEBPB. Similarities between provide insights into their clinical association.

Language: Английский

Citations

0