Placenta最新文献

{"title":"Exposure to Group B Streptococcus-induced chorioamnionitis alters the proteome of placental extracellular vesicles.","authors":"Seline Vancolen, Mathilde Chevin, Bernard Robaire, Guillaume Sébire","doi":"10.1016/j.placenta.2025.01.008","DOIUrl":"https://doi.org/10.1016/j.placenta.2025.01.008","url":null,"abstract":"<p><strong>Introduction: </strong>Group B Streptococcus (GBS) is an opportunistic pathogen that can induce chorioamnionitis (CA), increasing the risk of neurodevelopmental disorders (NDDs) in the offspring. The placenta facilitates maternal-fetal communication through the release of extracellular vesicles (EVs), which may carry inflammatory molecules such as interleukin (IL)-1. Although the role of EVs in immune modulation is well established, their specific characterization in the context of GBS-induced CA has not yet been investigated. Understanding placental-derived EVs could further define how IL-1 and other inflammatory factors contribute to NDDs.</p><p><strong>Methods: </strong>We used an established rat model of GBS-induced CA. EVs from control and GBS infected dams were isolated from placentas and characterized using nanoparticle tracking analysis and transmission electron microscopy. The protein content was assessed via mass spectrometry, followed by subsequent pathway analysis. ELISA was used to quantify cytokine levels.</p><p><strong>Results: </strong>GBS-infected placentas exhibited calcification and increased weight, while fetal weight decreased. Analysis of the proteome from control versus GBS placental EVs revealed distinct profiles, with many proteins involved in the innate immune response, including alarmins (S100A8/9), complement pathways, and cytokine signaling pathways. Pathway analysis highlighted IL-1α and IL-1β identified as key upstream regulators. Notably, EVs from GBS-infected males showed a 44-fold increase in intracellular IL-1β compared to controls.</p><p><strong>Discussion: </strong>These findings indicate that GBS-induced CA alters the protein content of EVs from placental cells. Our findings of increased IL-1β-associated EVs highlight the need for further investigation into the role of these cytokines from GBS-exposed placentas and their role in brain injuries leading to NDDs.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of senescence-associated transcripts in the human placenta.","authors":"Oren Barak, Alexander D Bauer, W Tony Parks, Tyler C Lovelace, Panayiotis V Benos, Tianjiao Chu, Yoel Sadovsky","doi":"10.1016/j.placenta.2025.01.009","DOIUrl":"https://doi.org/10.1016/j.placenta.2025.01.009","url":null,"abstract":"<p><strong>Introduction: </strong>Fusion of mononucleated cytotrophoblasts into syncytium leads to trophoblast senescence. Yet, premature senescence is associated with preeclampsia, fetal growth restriction (FGR), and related obstetrical syndromes. A set of 28 transcripts that comprise senescence-associated secretory phenotype (SASP) was recently described in placentas from women with preeclampsia. We posited that this transcript set is uniquely regulated in late-term placentas or in placentas derived from participants with major obstetrical syndromes.</p><p><strong>Methods: </strong>Using our large placental RNAseq bank, we analyzed data from healthy participants (n = 33) with histologically normal placentas, representing delivery at 37-41 weeks. To represent diseases, we included RNAseq data from participants (n = 220) with severe preeclampsia, FGR, FGR with a hypertensive disorder (FGR + HDP), or spontaneous preterm delivery, and healthy controls (n = 129). We also assessed the expression of several SASPs in primary human trophoblasts that were exposed in vitro to hypoxia, reduced differentiation, or ferroptotic or apoptotic signals.</p><p><strong>Results: </strong>Among the 28 SASP transcripts analyzed, eight had a significant change between deliveries at <37 weeks vs ≥ 41 weeks, including upregulation of FSTL3, IL1RL1, INHBA, and VEGFA and downregulation of STC1, RARRES2, MRC2, and SELP. The expression of SASP mRNAs was enriched in the placentas from the assessed syndromes, with most expression changes in placentas from FGR/HDP. Our in vitro analysis associated hypoxia or apoptosis with altered expression of FSTL3, VEGFA, and DKK1.</p><p><strong>Discussion: </strong>A set of placental SASPs defines late-term placentas, placental dysfunction-related clinical syndromes, and in vitro-defined trophoblast injury. Trophoblastic SASP signatures may assist in characterizing placental senescence in health and disease.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"161 ","pages":"31-38"},"PeriodicalIF":3.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The expression of chromosome 19 miRNA cluster members during insulin sensitivity changes in pregnancy.","authors":"Fernanda Alvarado-Flores, Tianjiao Chu, Patrick Catalano, Yoel Sadovsky, Perrie O'Tierney-Ginn","doi":"10.1016/j.placenta.2025.01.007","DOIUrl":"https://doi.org/10.1016/j.placenta.2025.01.007","url":null,"abstract":"<p><strong>Hypothesis: </strong>Declines in insulin sensitivity during pregnancy important for fetal growth are associated with impairments in skeletal muscle post-receptor insulin signaling. The primary initiator of these changes is unknown but believed to originate in the placenta. We hypothesize that placental miRNAs are associated with maternal sensitivity changes and impact insulin-sensitive mechanisms in target tissues in vitro.</p><p><strong>Methods: </strong>Using qPCR, miRNA expression was measured in plasma in early (12-16 wk) and late (34-36 wk) gestation (N = 39) and placental tissue at term (37-41 weeks) (N = 142) collected from independent cohorts. Insulin-sensitive glucose uptake was measured in human skeletal muscle myoblasts exposed to miRNA mimics in vitro. Multi-linear and binomial regression models were generated to test for associations between miRNAs, insulin sensitivity and fetal growth outcomes, adjusting for relevant clinical variables. P < 0.05 was considered significant.</p><p><strong>Results: </strong>Placental expression of chromosome 19 miRNA cluster (C19MC) members was higher in patients with obesity and positively correlated with maternal HOMA-IR (Homeostatic Model Assessment for Insulin Resistance; miR-516b-5p, miR-517a-3p, miR-1283). Placental expression of miR-517a-3p was higher in offspring with high adiposity and birthweight. Plasma miR-517a-3p in early and late pregnancy was related to decreases in insulin sensitivity during pregnancy. Mimics for miR-517a-3p and miR-524-3p both impaired insulin-sensitive glucose uptake in human skeletal myocytes in vitro.</p><p><strong>Discussion: </strong>Our findings based on data from two independent pregnancy cohorts and in vitro studies support a role for members of the C19 cluster of miRNAs - particularly miR-517a-3p - in physiological changes in insulin sensitivity over pregnancy, which may impact fetal growth.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"161 ","pages":"23-30"},"PeriodicalIF":3.0,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Congenital Chagas disease: The importance of Trypanosoma cruzi-placenta interactions.","authors":"Castillo Christian, Liempi Ana, Fernández-Moya Alejandro, Guerrero-Muñoz Jesús, Araneda Sebastian, Cáceres Gabriela, Alfaro Sebastián, Gallardo Christian, Maya Juan Diego, Müller Marioly, Kemmerling Ulrike","doi":"10.1016/j.placenta.2025.01.004","DOIUrl":"https://doi.org/10.1016/j.placenta.2025.01.004","url":null,"abstract":"","PeriodicalId":20203,"journal":{"name":"Placenta","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myeloperoxidase-mediated immature dendritic cell promotes vascular remodeling and functional placenta formation.","authors":"Feng Gao, Jiabin Jiang, Yunfeng Lin, Juan Tang, Yanqi Ke, Yuqing Zheng, Qingquan Chen, Qicai Liu","doi":"10.1016/j.placenta.2025.01.006","DOIUrl":"https://doi.org/10.1016/j.placenta.2025.01.006","url":null,"abstract":"<p><strong>Introduction: </strong>The distribution of myeloperoxidase (MPO) and dendritic cells (DCs) in sponge trophoblast cells may contribute to the syncytialisation of trophoblast cells and the establishment of uterine placental circulation. Our previous series of studies have shown that MPO plays an important role in angiogenesis and repair, and placental vascular dysfunction can lead to serious pregnancy complications and even miscarriage.</p><p><strong>Methods: </strong>Mouse model of MPO knockout was constructed, and the crosstalk between MPO and dendritic cells (DC) cells was investigated to determine whether MPO is involved in the pregnancy process. Abnormal decidual vasculogenesis in MPO^-/- pregnant mice was also suggested by RNA-seq analysis of uterine tissues from pregnant mice. In addition, we extracted mouse BMDC, analyzed the relationship between Mpo and BMDC, and established a co-culture system between BMCD and endothelial cells.</p><p><strong>Results: </strong>It was found that angiogenesis in the decidual tissue of MPO^-/- mice was impaired in early pregnancy, while in WT mice of the same pregnancy period, MPO and DC were observed to co-localize at the site of vascular development, it was found that immature BMDC can significantly promote the tube formation ability of endothelial cells in vitro, while MPO it is the key for BMDC to maintain immature phenotype.</p><p><strong>Discussion: </strong>In conclusion, our study reveals a new role of immature DCs induced by MPO in promoting vascular remodeling of decidual tissue and functional placental formation.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"161 ","pages":"1-13"},"PeriodicalIF":3.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association studies of vasoactive genes and preeclampsia in taiwan.","authors":"Mei-Lin Yang, Fong-Ming Chang, Meng-Hsing Wu, Chung-Hwan Chen, Tsung-Lin Cheng, Lin Kang","doi":"10.1016/j.placenta.2025.01.005","DOIUrl":"https://doi.org/10.1016/j.placenta.2025.01.005","url":null,"abstract":"<p><strong>Background: </strong>Preeclampsia (PE) is a serious condition characterized by hypertension and proteinuria after 20 weeks of gestation. The exact cause of PE is unknown but may involve abnormalities in the renin-angiotensin-aldosterone system (RAAS) and endothelial nitric oxide synthase (eNOS). Genetic variations in angiotensinogen (AGT), angiotensin-converting enzyme (ACE), and eNOS genes have been associated with PE. This study aimed to investigate the potential of vasoactive-related gene polymorphisms as indicators of susceptibility to preeclampsia in Taiwanese women.</p><p><strong>Methods: </strong>A total of 109 women with severe PE and 150 controls from the Taiwanese population were genotyped for specific vasoactive gene polymorphisms, including M235T and T174M polymorphisms of AGT gene, insertion/deletion (I/D) polymorphism in ACE gene, and G894T (Glu298Asp) polymorphism and 27bp variable number of tandem repeats (VNTR 3/4/5) polymorphism of the eNOS gene. The association between genotype and disease was assessed using Chi-square tests.</p><p><strong>Results: </strong>The study found no significant differences in the M235T and T174M polymorphisms of AGT gene between the PE and control groups. However, haplotype frequencies for the M235T and T174M polymorphisms exhibited a significant association with PE. The genotype distributions of the I/D polymorphism of ACE gene showed a significant difference between PE and control groups. Additionally, no significant differences were detected in the polymorphisms of the eNOS gene between PE and control groups.</p><p><strong>Conclusion: </strong>The findings of this study suggest that the AGT M235T-T174M haplotype and ACE insertion/deletion polymorphism may contribute to the development of preeclampsia and could serve as susceptibility markers for preeclampsia in Taiwanese women.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"161 ","pages":"14-22"},"PeriodicalIF":3.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Placental alkaline phosphatase (PLAP): Is it exclusively placental?","authors":"Awanit Kumar, Sourabh Sharma, Maged M Costantine, Kara Rood, Rheanna Urrabaz-Garza, Jeena Jacob, Lauren S Richardson, Ananth Kumar Kammala, Ramkumar Menon","doi":"10.1016/j.placenta.2025.01.001","DOIUrl":"https://doi.org/10.1016/j.placenta.2025.01.001","url":null,"abstract":"<p><strong>Background: </strong>Adverse pregnancies outcomes present a clinical dilemma in Perinatal medicine. This is partly due to lack of accuracy of current biomarkers to predict high-risk pregnancies at an earlier stage. The placental alkaline phosphatase (PLAP) carrying extracellular vesicles (EVs), and their cargo have been reported as a source of biomarkers for placental health and an indication of pre-eclampsia progression.</p><p><strong>Objectives: </strong>We postulate that PLAP is not only placental but also expressed in other fetal organs, suggesting that PLAP + ve EVs are not only a functional indicator of placental function alone.</p><p><strong>Methods: </strong>We evaluated PLAP in the placenta, fetal membranes, maternal decidua, myometrial cells, and the EVs derived from them. Various bioanalytical techniques were used to detect PLAP expressions in the cells and EVs. The EVs were characterized by size/quantity, PLAP as a cargo, and canonical EV protein markers.</p><p><strong>Results: </strong>PLAP expression was determined in the chorion trophoblast cells (CTCs) of the fetal membranes and the placental trophoblasts; however, it was absent in the amnion layer of the fetal membranes and the maternal uterine cells used in this study. Using multiple experimental approaches, we further verified the cellular sources of PLAP and confirmed that the EVs from the chorion and placental trophoblasts contain PLAP.</p><p><strong>Conclusion: </strong>Our studies suggest that PLAP is not truly placental. Instead, cells of trophoblast lineage in both fetal membranes and the placenta express PLAP in cells and their EVs. Although PLAP + ve EVs for biomarkers are not exclusively placental, they still represent real-time fetal-specific tissues conditions during pregnancy.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"160 ","pages":"118-125"},"PeriodicalIF":3.0,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142966333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The overview of lactylation in the placenta of preeclampsia.","authors":"Qiaoli Feng, Ping Yang, Jinli Lyu, Xinyang Liu, Shilin Zhong, Yiheng Liang, Ping Liu, Liting Huang, Shangrong Fan, Xiaowei Zhang","doi":"10.1016/j.placenta.2025.01.003","DOIUrl":"https://doi.org/10.1016/j.placenta.2025.01.003","url":null,"abstract":"<p><strong>Background: </strong>Preeclampsia is a major challenge for obstetricians due to its severe impacts on maternal and fetal health. Lysine lactylation (Kla) derived from lactate is a novel type of post-translational modification which has been confirmed to affect the malignant progression of diseases as an epigenetic modifier. However, the systemic lactylome profiling of preeclampsia is still unclear.</p><p><strong>Material and methods: </strong>Immunohistochemistry and protein immunoassay were performed on placenta tissues from preeclamptic patients and control pregnancies to compare lactylation levels between the groups. Then liquid chromatography-tandem mass spectrometry (LC-MS/MS) was utilized for quantitative lactylomic analysis and proteomic assessment for proteins with differentially lactated modification. Bioinformatics analyses were applied to reveal the conserved motif sequences and enrichment pathways.</p><p><strong>Results: </strong>Significant differences in protein lactylation levels were evident in the placenta between preeclamptic and control groups, with modifications observed in both histone and non-histone proteins. Lactylome analysis showed significant downregulation of 59 Kla proteins and 69 Kla sites in preeclamptic placentas, whereas 44 proteins and 60 sites were upregulated. These differentially lactylated proteins were primarily mitochondrial and associated with the citrate cycle (TCA cycle). Enriched metabolic pathways linked to lactylation included those important for vascular muscle contraction, platelet activation, and several signaling pathways like PI3K-Akt, PPAR, and cholesterol metabolism.</p><p><strong>Conclusions: </strong>Preeclamptic placentas exhibit distinct lactylation profiles compared to normal pregnancies, primarily affecting mitochondrial and TCA cycle-related energy metabolism. These changes contribute to the pathophysiology of preeclampsia by involving metabolic pathways critical for angiogenesis and endothelial function.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"160 ","pages":"135-143"},"PeriodicalIF":3.0,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of macrophage polarization by metformin through inhibition of TLR4/NF-κB pathway to improve pre-eclampsia.","authors":"Wei Shen, Qingfu Wang, Guofang Shen, Meiling Gu, Qifeng Shen, Ailan Zhang, Xiaohong Zhu","doi":"10.1016/j.placenta.2025.01.002","DOIUrl":"https://doi.org/10.1016/j.placenta.2025.01.002","url":null,"abstract":"<p><strong>Introduction: </strong>Pre-eclampsia (PE) is a pregnancy complication featuring hypertension and proteinuria. Metformin exerts clinically preventive effects on PE with an unspecified mechanism.</p><p><strong>Methods: </strong>Placental tissues from PE patients and normal pregnant (NP) women were collected. Twenty-four pregnant mice were divided into control, PE (40 μg/kg lipopolysaccharides (LPS)-induced modeling), aspirin, and metformin groups. After acquisition of bone marrow-derived macrophages (BMDM) and THP-1 cells, cells were categorized into control, LPS (100 ng/mL), metformin, and metformin + toll-like receptor 4 (TLR4) agonist RS 09 groups. Inflammatory factors and macrophage polarization were detected by ELISA, flow cytometry, immunofluorescence, immunohistochemistry, and qRT-PCR methods. TLR4/Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway protein expression was examined using Western blot.</p><p><strong>Results: </strong>Both PE patients and PE-like mice enhanced inducible nitric oxide synthase (iNOS), TLR4, p-NF-κB/NF-κB, and p-inhibitor of NF-κB (IκBα)/IκBα expression, and lower arginase 1 (Arg-1) expression. Moreover, metformin treatment in PE-like mice increased fetal number and weight and reduced hypertension, proteinuria, insulin resistance, tumor necrosis factor-α (TNF-α), IL-6, IL-1β, chemokine ligand 4 (CCL4), C-X-C motif chemokine ligand 2 (CXCL2) expression and M1 macrophage polarization, with similar inhibition to aspirin. In LPS-induced cells, metformin had the same effects mentioned above. Decreased TLR4, p-NF-κB/NF-κB, and p-IκBα/IκBα protein expression was caused by metformin both in vivo and in vitro. In vitro, RS 09 intervention inhibited anti-inflammatory and pro-M2 polarizing effects of metformin, activating TLR4/NF-κB pathway.</p><p><strong>Conclusion: </strong>Metformin may ameliorate PE by promoting M2 macrophage polarization through up-regulating TLR4/NF-κB pathway, laying theoretical basis for metformin clinical application in PE.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"160 ","pages":"89-99"},"PeriodicalIF":3.0,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferumoxytol-enhanced MRI of retroplacental clear space disruption in placenta accreta spectrum.","authors":"Andrew A Badachhape, Brian Burnett, Prajwal Bhandari, Laxman Devkota, Rohan Bhavane, Renuka Menon, Mayank Srivastava, Hennie Lombaard, Amir Shamshirsaz, Ketan B Ghaghada, Karin A Fox, Ananth V Annapragada","doi":"10.1016/j.placenta.2024.12.026","DOIUrl":"10.1016/j.placenta.2024.12.026","url":null,"abstract":"<p><strong>Introduction: </strong>Placenta accreta spectrum (PAS) occurs when the placenta is pathologically adherent to the myometrium. An intact retroplacental clear space (RPCS) is a marker of normal placentation. In this study, we investigate use of the FDA-approved iron supplement ferumoxytol for contrast-enhanced MRI of the RPCS in mouse models of normal pregnancy and PAS. We then demonstrate the translational potential of this technique in human patients (n = 6) presenting with severe PAS (FIGO Grade 3C), moderate PAS (FIGO Grade 1), and no PAS.</p><p><strong>Methods: </strong>T1-weighted sequences were used to determine the optimal dose of ferumoxytol in pregnant mice. Pregnant Gab3^-/- mice which demonstrate adherent placentation were imaged alongside wild-type (WT) pregnant mice with non-adherent placentation. Fe-MRI was also performed in 6 pregnant subjects using standard T1 and T2 weighted sequences and a 3D magnetic resonance angiography (MRA) sequence.</p><p><strong>Results: </strong>Ferumoxytol administered at 5 mg/kg led to strong placental enhancement in Fe-MRI images. Gab3^-/- mice demonstrated loss of the hypointense region characteristic of the RPCS relative to WT mice. In human patients, Fe-MRI enabled high uteroplacental vasculature signal and quantification of the volume and signal profile in severe and moderate invasion of the placenta relative to non-PAS cases.</p><p><strong>Discussion: </strong>Ferumoxytol, an FDA-approved iron oxide nanoparticle formulation, enabled T1w MRI visualization of abnormal vascularization and loss of uteroplacental interface in a murine model of PAS. The potential of this non-invasive visualization technique was then further demonstrated in human subjects and suggests the possibility of PAS diagnosis using contrast enhanced MRI.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"160 ","pages":"100-106"},"PeriodicalIF":3.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}