Placenta最新文献

{"title":"Regulation of macrophage polarization by metformin through inhibition of TLR4/NF-κB pathway to improve pre-eclampsia","authors":"Wei Shen ,&nbsp;Qingfu Wang ,&nbsp;Guofang Shen ,&nbsp;Meiling Gu ,&nbsp;Qifeng Shen ,&nbsp;Ailan Zhang ,&nbsp;Xiaohong Zhu","doi":"10.1016/j.placenta.2025.01.002","DOIUrl":"10.1016/j.placenta.2025.01.002","url":null,"abstract":"<div><h3>Introduction</h3><div>Pre-eclampsia (PE) is a pregnancy complication featuring hypertension and proteinuria. Metformin exerts clinically preventive effects on PE with an unspecified mechanism.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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 <em>in vivo</em> and <em>in vitro</em>. <em>In vitro</em>, RS 09 intervention inhibited anti-inflammatory and pro-M2 polarizing effects of metformin, activating TLR4/NF-κB pathway.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"160 ","pages":"Pages 89-99"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","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":"Platelet-derived factors modulate gene expression profile of human trophoblasts","authors":"Freya Lyssy ,&nbsp;Désirée Forstner ,&nbsp;Jacqueline Guettler ,&nbsp;Nadja Kupper ,&nbsp;Kaja Ujčič ,&nbsp;Stefan Wernitznig ,&nbsp;Lena Neuper ,&nbsp;Christine Daxboeck ,&nbsp;Amin El-Heliebi ,&nbsp;Julian C. Krappinger ,&nbsp;Julia Feichtinger ,&nbsp;Gerhard Cvirn ,&nbsp;Anna-Lena Hoebler ,&nbsp;Juergen Pollheimer ,&nbsp;Joanna L. James ,&nbsp;Martin Gauster","doi":"10.1016/j.placenta.2024.10.050","DOIUrl":"10.1016/j.placenta.2024.10.050","url":null,"abstract":"","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"160 ","pages":"Pages 151-152"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143377622","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":"Exploring organoid oviductal gland secretions for optimizing in vitro culture media: Insights from a bovine model","authors":"Sergio Navarro-Serna ,&nbsp;Eva González-Cantó ,&nbsp;Jon Romero-Aguirregomezcorta ,&nbsp;Ana Ferrero-Micó ,&nbsp;Maravillas Mellado-López ,&nbsp;Pilar Coy ,&nbsp;Vicente Pérez-García","doi":"10.1016/j.placenta.2024.10.062","DOIUrl":"10.1016/j.placenta.2024.10.062","url":null,"abstract":"","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"160 ","pages":"Pages 155-156"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143377864","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":"“Optimal timing for RNA isolation: Recommendations for placenta sample collection under clinical conditions”","authors":"J. Sommer ,&nbsp;L. Ehrlich ,&nbsp;A. Kühn ,&nbsp;K. Schellong ,&nbsp;R.C. Rancourt ,&nbsp;W. Henrich ,&nbsp;T. Braun","doi":"10.1016/j.placenta.2025.01.011","DOIUrl":"10.1016/j.placenta.2025.01.011","url":null,"abstract":"<div><div>In placenta research, tissue quality is essential for following laboratory investigations. In clinical settings with deliveries as an unpredictable factor, delayed sampling or incorrect storage until sampling is a common problem. Therefore, we set out to define time points for different storage conditions where good tissue quality is still achievable. RNA related parameters like 260/280-ratio, RNA integrity number (RIN) and gene expression were analyzed in 172 samples over a 24-h interval. We suggest a cut-off-point of 3-h after delivery of the placenta to ensure good tissue and RNA quality, especially when selecting genes with complex or low mRNA expression levels.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"161 ","pages":"Pages 52-54"},"PeriodicalIF":3.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143180535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactate promotes premature aging of preeclampsia placentas through histone lactylation-regulated GADD45A","authors":"Xiang Li ,&nbsp;Qianghua Wang ,&nbsp;Jiaojiao Fei ,&nbsp;Zhixin Jin ,&nbsp;Yue Wu ,&nbsp;Yafen Tao ,&nbsp;Chuanyue Jiang ,&nbsp;Xuegu Wang ,&nbsp;Nana Yang ,&nbsp;Biao Ding ,&nbsp;Chengli Dou","doi":"10.1016/j.placenta.2025.01.010","DOIUrl":"10.1016/j.placenta.2025.01.010","url":null,"abstract":"<div><h3>Background</h3><div>Premature placental aging has been linked to preeclampsia (PE), with lactate identified as a promoter of cellular senescence in various cell types. In this study, we explored the role and underlying mechanisms of lactate in driving premature placental aging associated with PE.</div></div><div><h3>Methods</h3><div>To evaluate senescence markers in placental samples or trophoblast cells, we conducted SA-β-Gal staining, western blotting, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and immunofluorescence assays. SiRNA transfection was used to reduce GADD45A expression in HTR-8/SVneo cells exposed to lactate. Additionally, chromatin immunoprecipitation-qPCR (ChIP-qPCR) was used to analyze histone lactylation at the GADD45A promoter region.</div></div><div><h3>Results</h3><div>SA-β-Gal staining indicated a significant increase in senescent cell proportions in placentas from PE patients compared to controls. Treatment with lactate enhanced senescence in trophoblast cells, leading to an increase in P16 expression. RNA sequencing analysis showed that genes differentially expressed in lactate-treated cells were involved in pathways linked to cellular senescence. Additionally, lactate augmented GADD45A expression and increased histone lactylation at its promoter region, while knocking down GADD45A in trophoblast cells mitigated the senescence induced by lactate.</div></div><div><h3>Conclusions</h3><div>Lactate promotes trophoblast senescence through epigenetic upregulation of GADD45A expression, offering fresh perspectives on the molecular mechanisms and potential treatment targets for PE.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"161 ","pages":"Pages 39-51"},"PeriodicalIF":3.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143180534","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":"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 ,&nbsp;Alexander D. Bauer ,&nbsp;W. Tony Parks ,&nbsp;Tyler C. Lovelace ,&nbsp;Panayiotis V. Benos ,&nbsp;Tianjiao Chu ,&nbsp;Yoel Sadovsky","doi":"10.1016/j.placenta.2025.01.009","DOIUrl":"10.1016/j.placenta.2025.01.009","url":null,"abstract":"<div><h3>Introduction</h3><div>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.</div></div><div><h3>Methods</h3><div>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 <em>in vitro</em> to hypoxia, reduced differentiation, or ferroptotic or apoptotic signals.</div></div><div><h3>Results</h3><div>Among the 28 SASP transcripts analyzed, eight had a significant change between deliveries at &lt;37 weeks <em>vs</em> ≥ 41 weeks, including upregulation of <em>FSTL3</em>, <em>IL1RL1</em>, <em>INHBA</em>, and <em>VEGFA</em> and downregulation of <em>STC1</em>, <em>RARRES2</em>, <em>MRC2</em>, and <em>SELP</em>. The expression of SASP mRNAs was enriched in the placentas from the assessed syndromes, with most expression changes in placentas from FGR/HDP. Our <em>in vitro</em> analysis associated hypoxia or apoptosis with altered expression of <em>FSTL3</em>, <em>VEGFA</em>, and <em>DKK1</em>.</div></div><div><h3>Discussion</h3><div>A set of placental SASPs defines late-term placentas, placental dysfunction-related clinical syndromes, and <em>in vitro-</em>defined trophoblast injury. Trophoblastic SASP signatures may assist in characterizing placental senescence in health and disease.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"161 ","pages":"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 ,&nbsp;Tianjiao Chu ,&nbsp;Patrick Catalano ,&nbsp;Yoel Sadovsky ,&nbsp;Perrie O'Tierney-Ginn","doi":"10.1016/j.placenta.2025.01.007","DOIUrl":"10.1016/j.placenta.2025.01.007","url":null,"abstract":"<div><h3>Hypothesis</h3><div>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 <em>in vitro</em>.</div></div><div><h3>Methods</h3><div>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 <em>in vitro</em>. 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 &lt; 0.05 was considered significant.</div></div><div><h3>Results</h3><div>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 <em>in vitro</em>.</div></div><div><h3>Discussion</h3><div>Our findings based on data from two independent pregnancy cohorts and <em>in vitro</em> 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.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"161 ","pages":"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 ,&nbsp;Jiabin Jiang ,&nbsp;Yunfeng Lin ,&nbsp;Juan Tang ,&nbsp;Yanqi Ke ,&nbsp;Yuqing Zheng ,&nbsp;Qingquan Chen ,&nbsp;Qicai Liu","doi":"10.1016/j.placenta.2025.01.006","DOIUrl":"10.1016/j.placenta.2025.01.006","url":null,"abstract":"<div><h3>Introduction</h3><div>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.</div></div><div><h3>Methods</h3><div>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 <em>MPO</em>^{<em>−/−</em>} 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.</div></div><div><h3>Results</h3><div>It was found that angiogenesis in the decidual tissue of <em>MPO</em>^{<em>−/−</em>} 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.</div></div><div><h3>Discussion</h3><div>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.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"161 ","pages":"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}