Placenta最新文献

{"title":"Fetal aorta assessment and cardiovascular biophysical indices in small for gestational age fetuses","authors":"Simou Maria,&nbsp;Sapantzoglou Ioakeim,&nbsp;Psarris Alexandros,&nbsp;Daskalaki Maria-Anastasia,&nbsp;Daskalakis Georgios","doi":"10.1016/j.placenta.2025.10.005","DOIUrl":"10.1016/j.placenta.2025.10.005","url":null,"abstract":"<div><h3>Background</h3><div>Cardiovascular disease ranks among the foremost causes of morbidity in adults and recent studies indicate that the process of atheromatosis appears to commence as early as fetal life. This study examined differences in several fetal aorta parameters between AGA and SGA fetuses.</div></div><div><h3>Methods</h3><div>This was a prospective cohort study that included a total of 198 women with singleton pregnancies, assessed between 31 and 34 weeks of gestation. Each fetus underwent a thorough assessment of its biometry and its Doppler indices. Concomitant examination of the fetal abdominal aorta diameter, aortic isthmus and aortic intima media thickness was included.</div></div><div><h3>Results</h3><div>AO D was significantly lower, while UA PI was significantly greater in SGA fetuses. The unadjusted regression coefficient of AO D on EFW centile was 1.33 while after adjusting for gestational age, UA PI and UtA PI it continued to be significantly associated with EFW centile (β = 1.49). The unadjusted regression coefficient of UA PI on EFW centile was −0.55 and after adjusting for gestational age and Ut A PI, it remained statistically significant and was demonstrated to be −0.60. Greater AO D was significantly associated with lower probability of EFW &lt;10th centile (OR = 0.87) and it remained significant after adjusting for gestational age and UtA PI (OR = 0.82).</div></div><div><h3>Conclusions</h3><div>The study demonstrated that AO D was significantly lower while UA-PI appeared significantly increased in SGA fetuses, remaining as such even after the appropriate adjustment. However, the study did not manage to show alterations in the rest of the fetal abdominal aorta measurements.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"171 ","pages":"Pages 188-193"},"PeriodicalIF":2.5,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145266782","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 downregulation of B2R inhibits spiral artery remodeling by reducing the autophagy of trophoblast cells.","authors":"Weichen Pan, Rongrong Zhu, Xiaoyu Wang, Zhiyin Wang, Dan Liu, Guangfeng Zhao, Mingming Zheng","doi":"10.1016/j.placenta.2025.10.001","DOIUrl":"https://doi.org/10.1016/j.placenta.2025.10.001","url":null,"abstract":"<p><p>Preeclampsia (PE) is a severe pregnancy complication characterized by hypertension and proteinuria after 20 weeks of gestation, posing significant risks to maternal and fetal health. Although its exact etiology remains unclear, inadequate trophoblast invasion and impaired remodeling of uterine spiral arteries are recognized as key contributors. The Bradykinin B2 receptor (B2R), a G protein-coupled receptor, was found to be downregulated in the placenta of early pregnancies that subsequently progress to PE. Our previous study has also shown that B2R can suppress the proliferation and migration of extravillous trophoblasts (EVT). However, the underlying mechanism remains elusive. By analyzing the transcriptome of HTR8 cells (an EVT cell line) with B2R knockdown, we found that B2R downregulation impairs autophagy in EVTs. Subsequently, we confirmed that autophagy is downregulated in EVTs from the placentas of patients with PE. In vitro experiments further demonstrated that B2R knockdown leads to defective autophagy in HTR8 cells, resulting in decreased cell proliferation, migration, and invasion capabilities. Activating autophagy can alleviate the functional abnormalities of EVT cells caused by B2R downregulation. Mechanistic exploration revealed that B2R knockdown inhibits autophagy through the activation of the Wnt signaling pathway. Furthermore, we generated trophoblast-specific B2R knockout mice and found that the placentas of these mice exhibited reduced autophagy, insufficient EVT invasion, and abnormal spiral artery remodeling. These findings suggest that B2R-regulated autophagy is crucial for proper trophoblast function and spiral artery remodeling. Our study highlights the potential of targeting autophagy as a therapeutic strategy for PE, providing new insights into the molecular mechanisms underlying this complex disorder.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"171 ","pages":"194-204"},"PeriodicalIF":2.5,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281003","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":"Corrigendum to \"Cyp19a1-Cre-EGFP: A placenta-specific Cre transgenic mouse model for targeted gene recombination in trophoblast cells\" [Placenta 168 (2025) 209-218].","authors":"Shu-Min Pan, Nian-Kun Chen, Xue-Yuan Li, Xiao-Zhen Xie, Xiong Cao, Zhi-Jian Wang","doi":"10.1016/j.placenta.2025.07.094","DOIUrl":"10.1016/j.placenta.2025.07.094","url":null,"abstract":"","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"170 ","pages":"16-17"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800009","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":"MALAT1 overexpression contributes to choriocarcinoma by binding with RBM10 and promoting p53 degradation.","authors":"Hui Li, Yan Feng, Panhong Fan, Xiaohui Chen","doi":"10.1016/j.placenta.2025.07.075","DOIUrl":"10.1016/j.placenta.2025.07.075","url":null,"abstract":"<p><strong>Background: </strong>Choriocarcinoma (CC), a highly aggressive and malignant subtype of gestational trophoblastic disease (GTD), arises from the dysregulated proliferation of trophoblastic cells, which normally mediate placental development during pregnancy. This study aimed to characterize the expression and functional significance of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a nuclear-enriched long non-coding RNA, in CC pathogenesis.</p><p><strong>Methods: </strong>We analyzed MALAT1 expression levels in 30 normal placental villi, 46 hydatidiform moles (repressive subtype), and 52 CC specimens. To identify MALAT1-interacting proteins, we performed RNA antisense purification followed by immunoblotting, with subsequent validation via co-immunoprecipitation (Co-IP) and immunofluorescence (IF) assays.</p><p><strong>Results: </strong>MALAT1 was significantly upregulated in CC tissues compared to controls. In vivo xenograft experiments further revealed that MALAT1 overexpression enhanced tumor growth. Mechanistically, we identified RNA-binding motif protein 10 (RBM10), a key spliceosomal regulator, as a novel MALAT1-binding partner. Strikingly, MALAT1 promoted p53 protein degradation without affecting its transcriptional levels, and this oncogenic effect was mediated through an RBM10-dependent mechanism.</p><p><strong>Conclusions: </strong>In conclusion, our findings establish MALAT1 as a critical oncogenic driver in CC, functioning through its interaction with RBM10 to destabilize p53 and accelerate tumor progression. These insights highlight the potential of the MALAT1-RBM10-p53 axis as a therapeutic target in CC.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"170 ","pages":"8-15"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800010","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 slice techniques in physiology, pathophysiology, and toxicology: A systematic review with a focus on precision-cut slices","authors":"H. Wang ,&nbsp;F.A. Elzinga ,&nbsp;A. Nagelkerke ,&nbsp;D.J. Touw ,&nbsp;F. Rozendaal ,&nbsp;L.A. Hillawie ,&nbsp;D. Haan ,&nbsp;B. Brook ,&nbsp;S.J. Gordijn ,&nbsp;J.R. Prins ,&nbsp;P. Olinga ,&nbsp;P. Mian","doi":"10.1016/j.placenta.2025.09.022","DOIUrl":"10.1016/j.placenta.2025.09.022","url":null,"abstract":"<div><div>Placental precision-cut tissue slices offer an advanced in vitro model that preserves tissue architecture and microenvironment, improving physiological relevance over traditional methods such as animal models and cell lines. This systematic review summarizes the methods and applications of placental slices in research.</div><div>A PRISMA-guided systematic review was conducted in PubMed and Embase to identify studies involving slicing techniques in placenta-related research published up to June 6, 2025. Primary articles using human or animal placental slices for culture were included. Key study variables, including study aims, placenta characteristics, slice techniques, culture conditions, viability assessments, and main findings were extracted and analyzed.</div><div>A total of 52 studies were included. Of these studies, 30 used human placenta (90.0 % from term pregnancies) and 24 used animal placentas (87.6 % late-term). Slicing methods were described in 33 studies, with 14 of those were manually prepared. The most commonly used culture condition was Krebs-Ringer bicarbonate buffer (36.5 %), combined with 95 % O₂ and 5 % CO₂ (79.5 %). Only eight studies conducted viability assessments, with histological morphology being the most frequently used approach. Based on research focus, the studies were categorized into physiological (69.2 %), pathophysiological (17.3 %), and toxicological (13.4 %) studies.</div><div>In conclusion, this review summarizes current applications of placental slicing techniques and highlights the methodological diversity across studies. The variability in approaches underscore the need for standardized protocols, while the collective evidence supports the use of placental slices as a promising model for investigating placental physiology, pathophysiology, and toxicology.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"171 ","pages":"Pages 150-177"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245008","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":"Dysregulation of placental mitochondrial structure dynamics and clearance in maternal obesity and gestational diabetes","authors":"Leena Kadam,&nbsp;Kaylee Chan,&nbsp;Ethan Tawater,&nbsp;Leslie Myatt","doi":"10.1016/j.placenta.2025.09.019","DOIUrl":"10.1016/j.placenta.2025.09.019","url":null,"abstract":"<div><h3>Introduction</h3><div>The placenta is exposed to an altered metabolic environment in obesity and gestational diabetes (GDM) leading to disruption in placental function. Mitochondria are critical for energy production and cellular adaptation to stress. We previously reported reduced trophoblast mitochondrial respiration in GDM. Here we examine changes in mitochondrial structure dynamics, quality and protein homeostasis as well as clearance in male and female placentas of pregnancies complicated by obesity and GDM. As obesity significantly increases the risk for GDM, our goal is to determine the distinct effects of each on placental mitochondria.</div></div><div><h3>Methods</h3><div>We collected placental villous tissue following elective cesarean section at term from lean (LN, pre-pregnancy BMI 18.5–24.9), obese (OB, BMI&gt;30) or obese with type A2 GDM women. Expression of proteins involved in mitochondrial biogenesis, structure dynamics, quality control and clearance were assessed by Western blotting. Significant changes between groups were determined in fetal sex-dependent and independent manner.</div></div><div><h3>Results</h3><div>Only placentas from obese women showed increase in proteins regulating mitochondrial biogenesis (PGC-1α and SIRT1). We report fetal sex-specific changes in mitochondrial fusion but an overall decline in fission in OB and GDM placentas. Both maternal obesity and GDM affected proteins involved in maintaining mitochondrial protein quality and genome stability. This was accompanied by a reduction in mitochondrial complexes, suggesting impaired mitochondrial function. Obesity led to partial activation of mitophagy pathways (e.g., increased PINK1 without PARKIN activation), but GDM placentas failed to mount this response.</div></div><div><h3>Discussion</h3><div>Obesity and GDM affect placental mitochondria through distinct complex sex-specific mechanisms that may contribute to altered mitochondrial function.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"171 ","pages":"Pages 140-149"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145221267","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":"Comparative proteomic analysis of placental trophoblasts from normotensive and preeclamptic pregnancies in response to vitamin D","authors":"Jie Xu ,&nbsp;Yang Gu ,&nbsp;Xinggui Shen ,&nbsp;David F. Lewis ,&nbsp;Dani Zoorob ,&nbsp;Yuping Wang","doi":"10.1016/j.placenta.2025.09.021","DOIUrl":"10.1016/j.placenta.2025.09.021","url":null,"abstract":"<div><h3>Background</h3><div>Vitamin D deficiency/insufficiency is a risk factor for preeclampsia. Vitamin D is known to support placental trophoblast function, yet the cellular and molecular mechanisms underlying trophoblast responses to vitamin D remain largely unclear. This study aims to characterize the protein expression profiles, signaling pathways, and cellular networks modulated by vitamin D in trophoblasts derived from normal and preeclamptic placentas.</div></div><div><h3>Study design</h3><div>Fourteen placentas were included in this study—seven from normal pregnancies and seven from preeclamptic cases. Trophoblasts were isolated and cultured with or without vitamin D. Vitamin D receptor expression was assessed using Western blot analysis. A gel-based proteomic assay combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze protein expression profiles. Functional enrichment and pathway analysis were performed using the PANTHER database.</div></div><div><h3>Results</h3><div>Distinct protein expression profiles and signaling pathways were observed between trophoblasts from normal and preeclamptic placentas in response to vitamin D. In normal trophoblast cells, vitamin D upregulated proteins associated with amino acid and fatty acid metabolism, etc. In preeclamptic trophoblasts, vitamin D upregulated proteins related to cytoskeletal dynamics and ATP metabolism. Notably, vitamin D downregulated MHC class I receptor-associated proteins in both normal and preeclamptic trophoblasts.</div></div><div><h3>Conclusion</h3><div>Vitamin D modulates a wide range of protein expression profiles and signaling pathways in trophoblasts, impacting key biological processes such as energy production, biosynthesis, metabolism, cell motility, and respiration. Importantly, vitamin D-mediated downregulation of MHC class I receptor activity suggests a potential role of vitamin D in promoting immune tolerance at the maternal-fetal interface.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"171 ","pages":"Pages 130-139"},"PeriodicalIF":2.5,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213092","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 placental pathology in Beckwith-Wiedemann Syndrome due to alterations in the KCNQ1OT1:TSS-DMR region","authors":"Sanam L. Kavari ,&nbsp;Andrew M. George ,&nbsp;Rebecca L. Linn ,&nbsp;Jennifer M. Kalish","doi":"10.1016/j.placenta.2025.09.020","DOIUrl":"10.1016/j.placenta.2025.09.020","url":null,"abstract":"<div><h3>Introduction</h3><div>Beckwith-Wiedemann Syndrome (BWS) is an imprinting disorder characterized by fetal and placental overgrowth. BWS is most often caused by genetic and epigenetic alterations involving the <em>KCNQ1OT1</em>-TSS:DMR (IC2) imprinting control region which alters expression of <em>CDKN1C</em> (p57KIP2). Here we report a cohort of patients with BWS primarily due to defects at IC2 compared to a well matched, non-BWS cohort to establish the placental features associated with these BWS subtypes.</div></div><div><h3>Methods</h3><div>This is a retrospective case-control study. Our cohort of 28 patients with BWS were matched to a non-BWS cohort of 28 unaffected patients. The rate of clinical and pathological features in the BWS and non-BWS cohorts were compared. Additionally, the associations between loss of p57KIP2 staining in the BWS cohort, placental pathology, and clinical outcomes were analyzed.</div></div><div><h3>Results</h3><div>We identified key pathological features in the placenta associated with BWS including placentomegaly, umbilical cord edema, abnormal chorionic vascular pattern, macroscopic cysts, stem villous stromal expansion, and abnormal extravillous trophoblast (EVT) morphology. We found that placental overgrowth in BWS is disproportionate to fetal overgrowth. We also identified associations between abnormal EVT morphology, loss of p57KIP2 staining, and rates of prematurity in patients with BWS.</div></div><div><h3>Discussion</h3><div>Novel features associated with BWS identified in this work can be used to inform the diagnosis of BWS when examining the placenta. Additionally, by establishing associations between adverse pregnancy outcomes and abnormal EVT morphology, we identified a potential mechanism for the increased risk of prematurity in pregnancies complicated by BWS.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"171 ","pages":"Pages 102-110"},"PeriodicalIF":2.5,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207389","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":"NNMT expression in preeclampsia: Analyses on placental tissues and cell lines","authors":"Giovanni Tossetta ,&nbsp;Roberto Campagna ,&nbsp;Sonia Fantone ,&nbsp;Nicoletta Di Simone ,&nbsp;Veronica Pompei ,&nbsp;Stefano Raffaele Giannubilo ,&nbsp;Andrea Ciavattini ,&nbsp;Davide Sartini ,&nbsp;Monica Emanuelli ,&nbsp;Daniela Marzioni","doi":"10.1016/j.placenta.2025.09.017","DOIUrl":"10.1016/j.placenta.2025.09.017","url":null,"abstract":"<div><h3>Objective</h3><div>Preeclampsia (PE) is a multisystem disorder characterized by new onset hypertension and proteinuria during pregnancy. Nicotinamide N-methyltransferase (NNMT) is an enzyme that catalyzes the N-methylation of nicotinamide (NAM) to form 1-methylnicotinamide (MNA) and S-adenosyl-L-homocysteine (SAH). The aim of this study was to investigate NNMT expression in normal and PE placentas, and evaluate whether hypoxia, oxidative stress and inflammation could modulate NNMT expression.</div></div><div><h3>Materials and methods</h3><div>Immunohistochemistry and Western blot were performed on first trimester, normal term and PE placentas. NNMT expression was also evaluated in HTR-8/SVneo and BeWo cell lines under hypoxic, oxidative stress (by H₂O₂) and inflammatory (by TNF-α) conditions.</div></div><div><h3>Results</h3><div>NNMT was expressed in cytotrophoblast and syncytiotrophoblast of first, third and PE placentas. Endothelial vessels were positive for NNMT expression in first and third trimester but mainly negative in PE placentas. NNMT expression did not change from first to third trimester but significantly decreased in PE placentas compared to control placentas. NNMT was expressed in the cytoplasm of both HTR-8/SVneo and BeWo cell lines, and its expression was not altered by syncytialization. Hypoxia decreased NNMT expression in BeWo but not HTR-8/SVneo cells while oxidative stress did not alter NNMT expression in both cell lines. TNF-α treatment significantly decreased NNMT expression in both cell lines.</div></div><div><h3>Conclusions</h3><div>Low NNMT expression found in PE placentas may represent a response to the hypoxia and inflammation featuring this disorder. Therefore, the enzyme could contribute to the normal human placental development, by defending trophoblast cells form PE-induced damages.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"171 ","pages":"Pages 111-120"},"PeriodicalIF":2.5,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207379","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":"Endothelial responses to angiogenic modulators highlight metabolic mechanisms underlying vascular dysfunction in preeclampsia","authors":"Priscila R. Nunes ,&nbsp;Ricardo M. Bruder ,&nbsp;Julyane N.S. Kaihara ,&nbsp;Fabio R. de Moraes ,&nbsp;Ljubica Tasic ,&nbsp;Raquel L. Bernardino ,&nbsp;Patricia Braga ,&nbsp;Pedro F. Oliveira ,&nbsp;Irene Rebelo ,&nbsp;Margarida Fardilha ,&nbsp;Ricardo C. Cavalli ,&nbsp;Valeria C. Sandrim ,&nbsp;Marco G. Alves","doi":"10.1016/j.placenta.2025.09.018","DOIUrl":"10.1016/j.placenta.2025.09.018","url":null,"abstract":"<div><h3>Introduction</h3><div>An elevated sFlt-1/PlGF ratio in preeclampsia (PE) directly impairs endothelial cell (EC) metabolism, leading to increased lactate dehydrogenase (LDH) release, lipid peroxidation, and mitochondrial dysfunction. This may reflect a distinct metabolite profile which correlates with systemic maternal metabolic dysregulation, as evidenced by the association between circulating sFlt-1 and succinate/glycine levels.</div></div><div><h3>Methods</h3><div>A cross-sectional case-control study was performed on plasma of PE patients (n = 54) in addition to an <em>in vitro</em> study using ECs. We correlated plasma metabolite profiles (by nuclear magnetic resonance-based metabolomics) with sFlt-1 levels (by Enzyme-Linked Immunosorbent Assay). Mechanistically, we examined the impact of varying sFlt-1/PlGF ratios on EC function and metabolism after 24 h, assessing cell viability, cytotoxicity, proliferation, oxidative stress-related damage (lipid peroxidation and nitration), and real-time mitochondria function and metabolic profiles.</div></div><div><h3>Results</h3><div>In pregnant women with PE, circulating sFlt-1 levels positively correlated with succinate and glycine levels, but not significantly with lactate or glucose. <em>In vitro</em>, as sFlt-1/PlGF ratios, increased EC damage (LDH release) and oxidative stress-related damage (4-hydroxy-2-nonenal) increased dose-dependently. High sFlt-1/PlGF ratios also increased mitochondrial spare respiratory capacity, suggesting a compensatory mechanism. Metabolomics revealed metabolic reprogramming in ECs exposed to varying sFlt-1/PlGF ratios, with significant alterations in lactate, succinate, glucose, and glycine levels.</div></div><div><h3>Discussion</h3><div>These correlations and <em>in vitro</em> changes suggest a mechanistic link between sFlt-1/PlGF ratios, oxidative stress-related damage, and metabolic reprogramming in ECs, which could be targeted for therapeutics. Furthermore, the identification of succinate and glycine as key metabolites associated with sFlt-1 levels and sFlt-1/PlGF ratios may provide novel biomarkers for disease risk stratification and/or monitoring PE progression.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"171 ","pages":"Pages 178-187"},"PeriodicalIF":2.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252266","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}