Placenta最新文献

{"title":"Tumor necrosis factor alpha inhibition improves fetal growth in a rat model of preeclampsia","authors":"Laura E. Coats ,&nbsp;Nathan Campbell ,&nbsp;Dylan Solise ,&nbsp;Gabrielle M. Chamoun ,&nbsp;Adam Z. Rawls ,&nbsp;Alexandra Demesa ,&nbsp;Ty Turner ,&nbsp;Baoying Zheng ,&nbsp;Barbara T. Alexander ,&nbsp;Babbette LaMarca","doi":"10.1016/j.placenta.2026.02.002","DOIUrl":"10.1016/j.placenta.2026.02.002","url":null,"abstract":"<div><h3>Introduction</h3><div>Tumor necrosis factor alpha (<strong>TNF-α</strong>) is elevated 2-fold in women with preeclampsia. Preclinical investigation shows TNF-α blockade reduces maternal blood pressure in reduced uterine perfusion pressure (<strong>RUPP</strong>) rats and attenuates the reduction in fetal weight. However, the benefits versus harms of this therapy on fetal growth and underlying pathogenesis are unknown. Thus, this study tested the hypothesis that maternal treatment with the soluble TNF-α inhibitor Etanercept (<strong>Etan</strong>) during late gestation improves placental perfusion, nutrient transport, and morphology, thereby improving fetal growth in the RUPP model of preeclampsia compared with Sham controls. We further hypothesized that maternal Etan treatment is associated with improved blood pressure and inflammatory profiles in offspring.</div></div><div><h3>Methods</h3><div>Sham or RUPP surgery was performed at gestational day (<strong>GD</strong>) 14, with vehicle or Etan (0.4 mg/kg, s.c.) administered at GD18.</div></div><div><h3>Results</h3><div>Fetal weight (p = 0.0365) and survival (p = 0.0002) were reduced in RUPP (<em>p</em> = 0.0365) at GD20; only fetal weight was improved in Etan-RUPP (p = 0.0480). At GD20, uterine artery resistance index (<strong>UARI</strong>) was increased in RUPP (p = 0.0094), but attenuated in Etan-RUPP, indicating improved placental perfusion. Impaired placental transport and morphology were evident in RUPP, with no improvement in Etan-RUPP. Birthweight was improved in Etan-RUPP (p = 0.0312), although total NK cells (p = 0.0376) were increased in female Etan-RUPP offspring. Circulating AT1-AA activity was elevated in adult male and female RUPP offspring (p = 0.0013, p = 0.0006), but attenuated in female Etan-RUPP offspring. <strong>Discussion</strong>: These results suggest improved fetal growth in Etan-RUPP, independent of placental morphology or nutrient transporter expression, with sex-specific effects on inflammation in adult RUPP offspring.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"176 ","pages":"Pages 22-30"},"PeriodicalIF":2.5,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146166388","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":"Single-cell atlas of the equine placenta reveals cellular heterogeneity and gestational-stage-associated programs","authors":"Margo H. Verstraete ,&nbsp;Jamie K. Norris ,&nbsp;Shavahn C. Loux ,&nbsp;Ward De Spiegelaere ,&nbsp;Mariano Carossino ,&nbsp;Peter Daels ,&nbsp;Pouya Dini","doi":"10.1016/j.placenta.2026.02.004","DOIUrl":"10.1016/j.placenta.2026.02.004","url":null,"abstract":"<div><h3>Introduction</h3><div>The placenta mediates critical interactions between mother and offspring that guide development and impact long-term health. Despite its importance, the cellular organization of the equine (<em>Equus caballus</em>) placenta remains poorly defined. The equine epitheliochorial placenta, characterized by the absence of trophoblast invasion and prominent endocrine activity, provides a unique comparative model for studying placental cellular composition and development.</div></div><div><h3>Methods</h3><div>We applied single-cell RNA sequencing to chorioallantois tissue collected from first-trimester (n = 1) and term (n = 2) equine placentas to generate a comprehensive cellular atlas across gestation.</div></div><div><h3>Results</h3><div>We identified four major fetal cell lineages: trophoblast, stromal, endothelial, and Hofbauer-like cells. Subclustering revealed ten transcriptionally distinct cell populations, highlighting previously unrecognized heterogeneity within trophoblast, stromal, and Hofbauer-like cells. Comparative analyses between first-trimester and term placentas demonstrated marked gestational-stage-associated differences in cellular composition and gene expression programs. The early-stage placenta was dominated by shared transcriptional signatures associated with growth, extracellular matrix organization, and cell cycle activity, whereas term placentas exhibited increased immune-related and tissue remodeling pathways and greater cell type-specific specialization.</div></div><div><h3>Discussion</h3><div>Together, this study provides the first high-resolution single-cell transcriptomic atlas of the equine placenta, offering fundamental insights into placental cellular diversity and developmental dynamics. This resource establishes a foundation for comparative placental biology and for investigating equine gestational disorders.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"176 ","pages":"Pages 13-21"},"PeriodicalIF":2.5,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146158069","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 dynamic interplay between insulin resistance and autophagy: Exploring the coordinated regulation of multiple pathways in the pathogenesis of miscarriage.","authors":"Jiayu Fang, Haixuan Lai, Zhaolan Zeng, Yuyuan Liu, Li Li, Shuang Qin","doi":"10.1016/j.placenta.2026.03.015","DOIUrl":"https://doi.org/10.1016/j.placenta.2026.03.015","url":null,"abstract":"<p><p>This narrative review summarizes recent advances in understanding the interrelationship among insulin resistance (IR), autophagy, and miscarriage. As a critical regulator of metabolic homeostasis, IR not only contributes to the development of various metabolic disorders but is also associated with an increased risk of miscarriage. IR elevates miscarriage risk through multiple mechanisms, including altering the intrauterine environment, modulating androgen levels, impairing mitochondrial function, enhancing oxidative stress, and activating inflammatory pathways via increased reactive oxygen species (ROS). Triggered by stressors like oxidative stress, autophagy regulates placental development and function through its effects on trophoblasts, macrophages, and decidualization, consequently, dysregulated autophagy can contribute to miscarriage. Furthermore, IR inhibits autophagic activity via activation of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway (through the PI3K-AKT axis), which suppresses ULK1. Chronic IR leads to oxidative stress (increased ROS) and mitochondrial dysfunction, which in turn promotes autophagy by inhibiting mTORC1 through the 5' adenosine monophosphate-activated protein kinase (AMPK) pathway. Moderate autophagy improves insulin sensitivity by removing damaged mitochondria and alleviating endoplasmic reticulum stress. However, excessive autophagy, such as in pancreatic β-cells, can degrade insulin granules and reduce insulin secretion, thereby exacerbating IR. This review explores the interactions among IR, autophagy and miscarriage, aiming to provide new insights for the prevention and treatment of miscarriage.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147654595","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":"Characterizing placental dysfunction with DNA methylation profiling and placental histopathology","authors":"Hannah J. Illing ,&nbsp;Alexa A. Freedman ,&nbsp;Ella O. Beraldo ,&nbsp;Lauren Keenan-Devlin ,&nbsp;Gregory E. Miller ,&nbsp;Ann E. Borders ,&nbsp;Wendy P. Robinson ,&nbsp;Linda M. Ernst","doi":"10.1016/j.placenta.2026.02.008","DOIUrl":"10.1016/j.placenta.2026.02.008","url":null,"abstract":"<div><h3>Background</h3><div>Placental pathology is associated with abnormal fetal growth and development. Altered placental DNA methylation (DNAme) has been associated with preeclampsia and fetal growth restriction but has not been well studied in the context of placental pathology, which likely underlies such changes. Our goal was thus to evaluate the association of DNAme with four major classes of placental pathology.</div></div><div><h3>Methods</h3><div>We utilized data from 484 placentas with both Illumina EPICv1 DNAme data and detailed histopathology information. Placental lesions were grouped as: acute inflammation (AI), chronic inflammation (CI), maternal vascular malperfusion (MVM), and fetal vascular malperfusion (FVM). We evaluated associations with DNAme based estimates of placental cell-types and epigenetic age acceleration, and used linear models to explore changes to autosome-wide DNAme with pathology.</div></div><div><h3>Results</h3><div>We identified 281 and 56 CpGs that were differentially methylated (FDR&lt;0.05, |Δβ|&gt;0.05) in association with high-grade MVM and high-grade FVM respectively. High-grade MVM and high-grade FVM were associated with increased and decreased estimates of syncytiotrophoblast respectively. There were no CpGs differentially methylated in association with the inflammation pathologies. Epigenetic age acceleration was not associated with any pathology, suggesting the placental epigenetic clocks are robust at estimating gestational age in the presence of pathology.</div></div><div><h3>Conclusions</h3><div>Changes in DNAme were associated with high-grade vascular pathologies, and DNAme may complement histopathologic placental examination. While changes largely reflected altered cell composition, altered gene regulation at the cellular level may also be present in these pathologies. Differential DNAme in high-grade MVM/FVM may contribute to or be a response to placental pathology.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"176 ","pages":"Pages 53-61"},"PeriodicalIF":2.5,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146191966","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":"scRNA-seq of preeclamptic trophoblasts identifies EBI3, COL17A1, miR-27a-5p, and miR-193b-5p as hypoxia markers: validation of neuradapt as a superior mimetic to cobalt chloride","authors":"Evgeny Knyazev ,&nbsp;Timur Kulagin ,&nbsp;Ivan Antipenko ,&nbsp;Alexander Tonevitsky","doi":"10.1016/j.placenta.2026.02.005","DOIUrl":"10.1016/j.placenta.2026.02.005","url":null,"abstract":"<div><h3>Background</h3><div>Preeclampsia (PE) complicates 2–8% of pregnancies and involves placental hypoxia and HIF-pathway activation, especially in early-onset PE (eoPE). Chemical mimetics like cobalt (II) chloride (CoCl₂) and oxyquinoline derivatives model trophoblast hypoxia <em>in vitro</em>, yet their fidelity in recapitulating PE gene profiles remains unclear. Integrating patient tissue analyses with experimental models may reveal common markers and validate physiologically relevant paradigms.</div></div><div><h3>Methods</h3><div>We analyzed scRNA-seq data from 10 eoPE, 7 late-onset PE, and matched control placentas, identifying villous cytotrophoblast, syncytiotrophoblast, and extravillous trophoblast (EVT). BeWo b30 cells were treated for 24 h with CoCl₂ (300 μM) or the oxyquinoline derivative neuradapt (5 μM) to induce hypoxia. RNA-seq with qPCR validation and small RNA-seq quantified mRNA and microRNA changes; PROGENy inferred pathway activities.</div></div><div><h3>Results</h3><div>scRNA-seq revealed highest hypoxia activation in eoPE, with EVT showing maximum activity. Nine genes were upregulated across all trophoblast types (<em>EBI3, CST6, FN1, RFK, COL17A1, LDHA, PKP2, RPS4Y1, RPS26</em>). <em>In vitro</em>, neuradapt induced more specific hypoxia responses than CoCl₂ (1284 vs. 3032 differentially expressed genes). Critically, <em>EBI3, FN1,</em> and <em>COL17A1</em> showed concordant upregulation in tissue and neuradapt-treated cells, whereas CoCl₂ produced opposite patterns. MicroRNAs hsa-miR-27a-5p and hsa-miR-193b-5p were consistently elevated in both models; 3′-isoforms of hsa-miR-9-5p and hsa-miR-92b-3p were identified as hypoxia-associated.</div></div><div><h3>Conclusions</h3><div><em>EBI3, COL17A1,</em> miR-27a-5p, and miR-193b-5p emerge as trophoblast hypoxia markers. Neuradapt (a selective HIF-prolyl hydroxylase inhibitor) provides a more physiologically relevant <em>in vitro</em> model than CoCl₂, recapitulating transcriptomic signatures observed in PE placentas. This integrated approach advances understanding of PE pathophysiology and therapeutic targeting.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"176 ","pages":"Pages 1-12"},"PeriodicalIF":2.5,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146158113","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 mapping of patients with birth weights below the third percentile","authors":"Maëlig Abgral ,&nbsp;Sophie Prévot ,&nbsp;Céline Desconclois ,&nbsp;Alexandra Benachi ,&nbsp;Alexandre J. Vivanti","doi":"10.1016/j.placenta.2026.02.001","DOIUrl":"10.1016/j.placenta.2026.02.001","url":null,"abstract":"<div><h3>Background</h3><div>Fetal growth restriction (FGR) is a frequent diagnosis with multiple etiologies (maternal, fetal, environmental) for which the placenta can be involved. A postnatal etiological work-up, such as placental pathology analysis, can help to identify the etiology of FGR and implement measures to prevent recurrence in a subsequent pregnancy.</div></div><div><h3>Objective</h3><div>The aim of this study is to unravel and provide an update on the mapping of possible placental lesions in the context of hypotrophic birth (below the third percentile).</div></div><div><h3>Method</h3><div>This is a single-center retrospective observational cohort study, in a tertiary care maternity (Antoine Béclère Hospital, Clamart, France). Inclusion criteria were: singleton pregnancy, live-born neonate, delivery between January 2014 and December 2018, birthweight below the 3rd percentile according to Audipog curves. Data from placental anatomopathological analysis were collected and analyzed using Amsterdam criteria.</div></div><div><h3>Results</h3><div>Among 733 eligible pregnancies, 585 placentas (79.8%) underwent pathological examination. At least one lesion of maternal vascular malperfusion (MVM) was identified in 75.6% of cases. The most frequent findings were placental hypoplasia (64.6%), accelerated villous maturation (18.5%), and placental infarctions (12.5%). A progressive decrease in birth weight was observed with increasing numbers of MVM criteria.</div></div><div><h3>Conclusion</h3><div>MVM lesions are highly prevalent in severe neonatal hypotrophy and correlate with disease severity. Placental pathological examination is a key component of the etiological work-up of FGR and may guide management and preventive strategies in subsequent pregnancies.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"176 ","pages":"Pages 62-67"},"PeriodicalIF":2.5,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146191967","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":"METTL3-regulated m6A modification modulates autophagy of placental mesenchymal stem/stromal cell by YTHDF3-mediated degradation of LncRNA GAS5 in preeclampsia","authors":"Yang Zhang,&nbsp;Di Wu,&nbsp;Li Zou,&nbsp;Xiangwei Cheng,&nbsp;Xiaoxia Liu","doi":"10.1016/j.placenta.2026.01.017","DOIUrl":"10.1016/j.placenta.2026.01.017","url":null,"abstract":"<div><h3>Background</h3><div>Preeclampsia (PE) causes maternal and perinatal morbidity through defective placental vascularization. Autophagy enhances placental mesenchymal stem/stromal cells (PMSC) proangiogenic properties while autophagy is reduced in PE. Long non-coding RNA GAS5, elevated in PE placenta, suppresses endothelial angiogenesis. N⁶-methyladenosine (m⁶A) modification through METTL3 regulates RNA stability and autophagy. However, regulatory mechanisms governing PMSC autophagy in PE remain unclear.</div></div><div><h3>Method</h3><div>Placenta specimens and PMSC from the normal and PE were compared. Molecular analyses included qRT-PCR, Western blotting, and m⁶A level evaluation. Transfections used siRNA knockdown and plasmid overexpression with rescue experiments. Autophagy was evaluated through LC3-II/LC3-I ratios and p62. Cellular functional assessments comprised CKK8 assays, ELISA for VEGF secretion, and tube formation for angiogenesis. MeRIP-PCR, RNA pull-down assay and RNA immunoprecipitation PCR identified m⁶A-modified transcripts.</div></div><div><h3>Result</h3><div>PE placenta and PMSC demonstrated significantly reduced METTL3 expression and global m⁶A modification levels, accompanied by elevated GAS5 expression. METTL3 overexpression enhanced PMSC autophagy, cell proliferation, VEGF secretion, and angiogenic capacity, while GAS5 exhibited opposing effects. GAS5 knockdown rescued PMSC autophagy and dysfunction caused by METTL3 deficiency. Mechanistically, METTL3 catalyzed m⁶A modification of GAS5 transcripts, facilitating YTHDF3-mediated recognition and degradation. YTHDF3 depletion reversed METTL3-induced autophagy improvements, confirming the regulatory cascade.</div></div><div><h3>Conclusion</h3><div>Our findings establish a novel epigenetic regulatory network wherein METTL3/YTHDF3-mediated GAS5 degradation controls PMSC autophagy in PE. This pathway represents a potential therapeutic target for ameliorating placental vascularization defects in PE.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"176 ","pages":"Pages 31-42"},"PeriodicalIF":2.5,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146181749","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":"Ultrastructural analysis of bovine trophoblast giant cells during their migration by serial block-face scanning electron microscopy (SBF-SEM).","authors":"Louiza Tiedje, Sophia Pankoke, Julia Hollenbach, Rüdiger Koch, Christoph Wrede, Christiane Pfarrer","doi":"10.1016/j.placenta.2026.03.012","DOIUrl":"https://doi.org/10.1016/j.placenta.2026.03.012","url":null,"abstract":"<p><p>Bovine trophoblast giant cells (TGC) are continuously formed and migrate towards the uterine epithelium (ME) to fuse with ME cells. To date it is not clear whether TGC differentiate from any uninucleate trophoblast cell and how exactly the migration works, because most data is based on two-dimensional images, generated by conventional transmission electron microscopy (TEM) with little opportunity for serial sections. Since the serial block face scanning electron microscopy (SBF-SEM) technique allows complete reconstruction of specifically selected tissue regions, we aimed to study TGC morphology and life cycle in relation to the feto-maternal interface in a three-dimensional setting. Placentome samples from six cows at different gestational stages were visualized by SBF-SEM (Zeiss Merlin VP Compact SEM with Gatan 3view2XP). The software Microscopy Image Browser was used for image processing, manual segmentation and analysis, while the software package IMOD was used for visualization. Here, TGC were divided morphologically into young, maturing and mature cells. A surprisingly high number of TGC still possessed contact with the fetal basement membrane (FBM). Young TGC had extensive contact to the FBM, while in maturing and mature TGC the contact occupied only small areas. In mid gestation, many TGC held simultaneous contact to the FBM and the ME (41-93%), which declined to 10% near term. To conclude, by adding a third dimension, SBF-SEM technology has questioned previous assumptions about TGC and hybrid cells and provides valuable new information about cell contacts and characteristics of bovine trophoblast cells.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147609393","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":"Emerging ultrasound-based imaging of the placenta during complications of pregnancy.","authors":"Lili Shi, Claudia I García Zorba, Miller A Dickerson, Carolyn L Bayer","doi":"10.1016/j.placenta.2026.03.011","DOIUrl":"10.1016/j.placenta.2026.03.011","url":null,"abstract":"<p><p>The placenta is an essential organ that develops throughout pregnancy, facilitating the exchange of nutrients, waste products, hormones, and antibodies between the fetal and maternal circulations. Insufficient development of placental structure and function is associated with various pregnancy disorders, including preeclampsia (PE), fetal growth restriction (FGR), gestational diabetes mellitus, preterm birth, and potential fetal cardiovascular diseases. Analyzing the spectrum of placental pathology in both normal and abnormal placentas helps to better understand disease pathologies and reduce maternal and fetal morbidity and mortality. Acoustic imaging techniques have been demonstrated as promising noninvasive methods for efficiently evaluating placental impairment. Ultrasound imaging (US) and Doppler ultrasound are standard modalities for assessing placental anatomy and gross morphology, due to their accessibility, affordability, and lack of ionizing radiation exposure. Preclinical studies provide opportunities to develop new acoustic-based imaging technologies. For example, using conventional US data, quantitative ultrasound (QUS) has been used to evaluate microstructural changes in placental tissue noninvasively. Shear-wave elastography (SWE) can provide diagnostic information about placental elasticity, reflecting tissue stiffness and biomechanical properties. Photoacoustic Imaging (PAI) provides valuable insights into placental hypoxia and inadequate vascular remodeling. Contrast-enhanced ultrasound (CEUS) and contrast-enhanced photoacoustic imaging (CEPA) can enable quantification of molecular expression changes in the placenta. In this article, we review major placental-related diseases and their potential consequences, as well as preclinical acoustic imaging modalities that hold potential for improving the assessment of placental health during pregnancy.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147491592","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":"METTL3-mediated N6-methyladenosine modification of LEPR is critical for fetal growth restriction","authors":"Dianjie Li ,&nbsp;Jiayi Jiang ,&nbsp;Yixiang Zhong ,&nbsp;Manling Luo ,&nbsp;Jianhong Chen ,&nbsp;Jing Li ,&nbsp;Xiangli Chen ,&nbsp;Meng Li ,&nbsp;Mei Zhong ,&nbsp;Yi Zhang","doi":"10.1016/j.placenta.2026.01.013","DOIUrl":"10.1016/j.placenta.2026.01.013","url":null,"abstract":"<div><h3>Introduction</h3><div>Fetal growth restriction (FGR) is one of the most common perinatal complications. The specific molecular mechanism remains undefined. N6-methyladenosine (m⁶A), the most common RNA modification in eukaryotes, is known to be associated with a variety of diseases. However, the relationships among METTL3, m⁶A and FGR have not been clearly reported.</div></div><div><h3>Methods</h3><div>The expression of METTL3, downstream target-leptin receptor (LEPR) and m⁶A modification level were compared between placentas of FGR and those of normal pregnancies. C57BL/6 pregnant mice were intraperitoneally injected with the METTL3-specific inhibitor STM2457 to analyze the effects of METTL3-associated m⁶A methylation. Changes downstream of METTL3 were determined by RNA sequencing. The regulatory relationships among METTL3, m⁶A, and LEPR were explored by cell migration assay, invasion assay, CCK8 assay, Western blotting and MeRIP‒qPCR.</div></div><div><h3>Results</h3><div>METTL3, LEPR and m⁶A modification were significantly decreased in the placenta of patients with FGR. After STM2457 treatment, adverse pregnancy outcomes and the FGR phenotype of fetal mice were observed. RNA-seq revealed that the downstream target of METTL3 was LEPR. The expression of LEPR was positively correlated with that of METTL3 via in vitro cellular mechanism experiments. The m⁶A modification level of LEPR was decreased when METTL3 was knocked down and increased when METTL3 was overexpressed. Furthermore, METTL3 and LEPR can separately or collectively promote the proliferation, migration and invasion of trophoblasts likely through m⁶A modification.</div></div><div><h3>Discussion</h3><div>Our study revealed that METTL3 regulated trophoblastic function likely through an m⁶A-LEPR-dependent mechanism in HTR8/SVneo cells and identified a potential biomarker panel for treatment prediction in FGR.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"175 ","pages":"Pages 54-65"},"PeriodicalIF":2.5,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146080312","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}