Placenta最新文献

{"title":"Placental weight as a predictor of future health: Insights from a large-scale genome-wide association study","authors":"Qinyi Zhang ,&nbsp;Tianhan Xu ,&nbsp;Sihui Yu ,&nbsp;Sufang Wu ,&nbsp;Ye Yang ,&nbsp;Hao Wu ,&nbsp;Jiawen Zhang","doi":"10.1016/j.placenta.2025.03.006","DOIUrl":"10.1016/j.placenta.2025.03.006","url":null,"abstract":"<div><h3>Introduction</h3><div>Placental weight has been associated with various adult-onset diseases, but the causal relationships and underlying mechanisms remain unclear.</div></div><div><h3>Methods</h3><div>This two-sample Mendelian randomization (MR) study utilized genome-wide association study (GWAS) data from multiple independent cohorts, primarily of European ancestry. The analysis included over 1.8 million individuals for type 2 diabetes mellitus (T2DM) outcomes. Data from four independent cohorts were used for validation. The inverse variance-weighted method was used for primary analysis, with weighted median, weighted mode, and MR-Egger regression for sensitivity analyses.</div></div><div><h3>Results</h3><div>Each standard deviation increase in genetically predicted placental weight was associated with T2DM (β = −0.109, 95 % CI: −0.184 to −0.034), basal cell carcinoma (β = 0.130, 95 % CI: 0.016 to 0.245), acute upper respiratory infections (β = −0.062, 95 % CI: −0.113 to −0.011), neurological diseases (β = −0.009, 95 % CI: −0.014 to −0.003), and endometrial cancer (β = −0.561, 95 % CI: −0.961 to −0.161). Placental weight also showed significant negative associations with blood glucose levels (β = −0.102, 95 % CI: −0.200 to −0.004). Mediation analyses revealed that dried fruit intake mediated 14.68 % of the total effect on T2DM risk, while immune cell phenotype analysis identified HLA DR on CD33dim HLA DR + CD11b + as a potential mediator in the causal pathway.</div></div><div><h3>Conclusion</h3><div>This study provides genetic evidence for a causal relationship between placental weight and T2DM risk, mediated partly through dietary habits and immune pathways. These findings suggest that early-life placental development may influence long-term metabolic health, highlighting the importance of prenatal care in preventing adult-onset diseases.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"164 ","pages":"Pages 10-20"},"PeriodicalIF":3.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619235","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":"Development and validation of a risk prediction model for placental abruption in patients with preeclampsia","authors":"Mei Yang,&nbsp;Menghui Wang,&nbsp;Qing Zhu,&nbsp;Nanfang Li","doi":"10.1016/j.placenta.2025.03.005","DOIUrl":"10.1016/j.placenta.2025.03.005","url":null,"abstract":"<div><h3>Introduction</h3><div>To develop a validated risk prediction model for placental abruption in preeclamptic patients with singleton pregnancies firstly.</div></div><div><h3>Methods</h3><div>Data from 1448 preeclamptic patients with singleton pregnancies who delivered between January 2013 and December 2022 were reviewed. Variables, including demographic characteristics, laboratory test results, comorbidities, and aspirin use were collected and analyzed. The preeclamptic patients were divided into a training set and a validation set according to the time of delivery. Logistic regression with a backward stepwise elimination method was used for variable screening and nomogram construction. The area under the receiver operating characteristic curve and calibration curve were used to evaluate its accuracy. Decision curve analysis and clinical impact curves were conducted to assess predictive performance.</div></div><div><h3>Results</h3><div>Finally, 1448 preeclamptic patients were included. We collected 50 variables for further analysis. Multivariate logistic regression analysis revealed that severity, subtype, premature rupture of membranes, urinary casts, diastolic blood pressure, aspartate aminotransferase, serum potassium, and fibrin degradation product levels were predictors of placental abruption. These factors were used to construct the nomogram model, which showed good concordance and accuracy. The area under the receiver operating characteristic curve values of the training set and the validation set were 0.767 (95 % CI = 0.728–0.806, P &lt; 0.001) and 0.800 (95 % CI = 0.728–0.872, P &lt; 0.001). Calibration curves revealed significant agreement between the nomogram model and actual observations. Receiver operating characteristic curve analysis and decision curve analysis indicated that the nomogram had good predictive performance.</div></div><div><h3>Discussion</h3><div>The prediction model can accurately estimate the risk of placental abruption in preeclamptic patients.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"164 ","pages":"Pages 1-9"},"PeriodicalIF":3.0,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143609710","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":"METTL3 suppressing SLC31A1 m6A modification regulates trophoblast migration and invasion","authors":"Song Wang ,&nbsp;Yixiong Lin ,&nbsp;Qiong Deng ,&nbsp;Xinyang Shen ,&nbsp;Qian Chen ,&nbsp;Xiaojing Yue ,&nbsp;Zhijian Wang","doi":"10.1016/j.placenta.2025.03.004","DOIUrl":"10.1016/j.placenta.2025.03.004","url":null,"abstract":"<div><h3>Objective</h3><div>This article aims to explore the mechanism of METTL3-mediated SLC31A1 N6-methyladenosine (m⁶A) modification affecting trophoblast migration and invasion in preeclampsia (PE).</div></div><div><h3>Methods</h3><div>The PE model was established using N-nitro-arginine methyl ester induction. Blood pressure was measured on gestation day (GD) 0, 5, 10, 15, and 20, and urine protein concentration on the day before mating and GD 20. HTR-8 SV/neo cells were cultured <em>in vitro</em> and treated with si-METTL3, oe-METTL3, oe-SLC31A1, si-SLC31A1, or RSM3 (METTL3 inhibitor). METTL3 and SLC31A1 were detected by immunohistochemistry and Western blot. After corresponding treatment, HTR-8SV/neo cells were measured for viability, cell damage, proliferation, migration and invasion and apoptotic rate. m⁶A modification level was measured by methylated RNA immunoprecipitation while the interactions between METTL3 and SLC31A1 mRNA, and YTHDF2 and SLC31A1 mRNA was determined by RNA immunoprecipitation.</div></div><div><h3>Results</h3><div>PE rats showed elevated METTL3 and down-regulated SLC31A1 expression. Treatment with si-METTL3 or oe-SLC31A1 suggested increased cell viability, proliferation, migration and invasion, and reduced cell damage and apoptosis rate, while cells treated with oe-METTL3 or si-SLC31A1 had reversed results. Up-regulating SLC31A1 partially reversed the inhibitory effect of METTL3 on HTR-8SV/neo cell migration and invasion. METTL3 reduced SLC31A1 mRNA stability and inhibited SLC31A1 expression through m⁶A modification in a YTHDF2-dependent manner. Furthermore, the <em>in vivo</em> experiments confirmed that METTL3 promotes PE progression through m⁶A methylation of SLC31A1.</div></div><div><h3>Conclusion</h3><div>METTL3 reduces SLC31A1 mRNA stability and down-regulates its expression in an m⁶A-YTHDF2-dependent manner, thereby inhibiting trophoblast migration and invasion.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"164 ","pages":"Pages 21-30"},"PeriodicalIF":3.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628055","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":"Expression of co-signaling molecules TIM-3/Galectin-9 at the maternal-fetal interface","authors":"Jingliang Xu ,&nbsp;Xuqing He ,&nbsp;Sujuan Zhang ,&nbsp;Li Li ,&nbsp;Penghao Li","doi":"10.1016/j.placenta.2025.03.002","DOIUrl":"10.1016/j.placenta.2025.03.002","url":null,"abstract":"<div><h3>Introduction</h3><div>During early pregnancy, fetal placental tissue implants into maternal decidual tissue, forming a unique interface where maternal immune cells do not reject the invading fetal cells. Given the roles of Galectin-9 and Tim-3 in tumor immune regulation, studying their distribution and function at this interface may provide insights into recurrent pregnancy loss.</div></div><div><h3>Methods</h3><div>This study uses single-cell transcriptomics, spatial transcriptomics, and multiplex immunohistochemistry to examine the expression and localization of Galectin-9 and TIM-3. Hormone-induced decidualization of immortalized human endometrial stromal cells was conducted to investigate Galectin-9 expression.</div></div><div><h3>Results</h3><div>The major immune cells in the maternal decidua, such as T cells, NK cells, and macrophages, co-express Galectin-9 and TIM-3. Unlike TIM-3, Galectin-9 is also highly expressed in endothelial cells and decidualized stromal cells. Among placenta-derived cells, Hofbauer cells (HBs) and Placenta-associated maternal monocytes/macrophages (PAMMs) exhibit high expression of both Galectin-9 and TIM-3, while trophoblast cells show relatively low levels of expression. Additionally, hormone-induced decidualization significantly upregulates Galectin-9 expression in endometrial stromal cells.</div></div><div><h3>Discussion</h3><div>The research results suggest that Galectin-9 and TIM-3, as important immune co-signaling molecules, may play a crucial role in maintaining the immune-tolerant microenvironment at the maternal-fetal interface. Additionally, the association between decidualization and Galectin-9 expression reveals its potential role in pregnancy maintenance, providing new insights for the study of adverse pregnancy outcomes.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"163 ","pages":"Pages 43-50"},"PeriodicalIF":3.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578901","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":"Maternal immune activation elicits rapid and sex-dependent changes in gene expression and vascular dysfunction in the rat placenta","authors":"Erin Biggar ,&nbsp;Ruth Thomas ,&nbsp;Megan L. Lave ,&nbsp;Gargi Jaju Bhattad ,&nbsp;Nagalingam Rajakumar ,&nbsp;Stephen J. Renaud","doi":"10.1016/j.placenta.2025.03.001","DOIUrl":"10.1016/j.placenta.2025.03.001","url":null,"abstract":"<div><h3>Introduction</h3><div>Maternal immune activation (MIA), characterized by increased circulating inflammatory mediators during pregnancy, is associated with adverse pregnancy outcomes and neurodevelopmental deficits in offspring. These health outcomes often manifest differently depending on fetal-placental sex. A well-established model of MIA involves administration of a viral mimetic, polyinosinic:polycytidilic acid (PolyI:C), to pregnant rodents. Placental responses to PolyI:C contribute to the detrimental effects of MIA on offspring, but these responses have not yet been well characterized. In the present study, we profiled acute gene expression changes in male and female placentas following PolyI:C administration to pregnant rats during late gestation.</div></div><div><h3>Methods</h3><div>Pregnant rats received 4 mg/kg PolyI:C or saline intravenously on gestational day 18.5, and tissues were harvested 4–5 h later. Gene expression profiling on placental tissue was performed. Enzyme immunoassays and immunohistochemistry were conducted to determine levels of select proteins in maternal blood and placental tissue, respectively.</div></div><div><h3>Results</h3><div>Maternal PolyI:C exposure caused a robust increase in levels of inflammatory mediators in maternal blood and placental tissue. There were more genes differentially expressed in female placentas after PolyI:C exposure (765) than male placentas (221), including reduced expression of genes associated with maternal-fetal communication. Placentas also had increased expression of genes linked with vascular dysfunction after PolyI:C-induced MIA.</div></div><div><h3>Discussion</h3><div>PolyI:C elicited a powerful inflammatory response in the placenta along with vascular dysfunction, likely contributing to the adverse pregnancy outcomes triggered by MIA. Female placentas responded to PolyI:C more vigorously than male placentas, which could underlie the differential outcomes of MIA depending on sex.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"163 ","pages":"Pages 51-60"},"PeriodicalIF":3.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600845","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":"Prediction of clinical risk factors in pregnancy using optimized neural network scheme","authors":"C. Jeyalakshmi ,&nbsp;G. Bhavani","doi":"10.1016/j.placenta.2025.03.003","DOIUrl":"10.1016/j.placenta.2025.03.003","url":null,"abstract":"<div><div>Women should be aware of prenancy related health issues. A user-friendly model is developed in which the patients can use as well as clinicians to determine the risks associated with foetal development inside the womb, birth weight, whose effects are typically linked to the mother through biological relationships. Recent advances in computer vision and artificial intelligence offer new techniques for automated evaluation of medical images across a variety of fields, including ultrasound (US) images. Enhancing the detection of the estimated foetal weight (EFW) and mother-foetal disease computations can aid obstetricians in making decisions and reduce perinatal issues. This study aims to build a birth weight classification and prediction of relevant parameters during delivery. In this data analysis suite, exploratory data analysis is performed as part of the data pre-processing to investigate the fundamental information and transformational properties. For feature extracting model, the Advanced Dynamic based Feature Selection (ADFS) algorithm has been used which is optimized using the enriched elephant herding optimization algorithm (EEHOA). The multiple feature estimation is classified using augmented recurrent neural network classifier (AURNN). The findings of analyses with graphical representations have been interpreted through the application of visual analytical techniques.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"163 ","pages":"Pages 33-42"},"PeriodicalIF":3.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578900","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 placental transcriptomic profile determined by maternal COVID-19 disease encompasses alterations reminiscent of preeclampsia","authors":"Ana Medel-Martinez ,&nbsp;Mark Strunk ,&nbsp;Alberto Cebollada-Solanas ,&nbsp;Laura Puente-Santamaría ,&nbsp;Sonia Gómez-Muñoz ,&nbsp;Marta Fabre ,&nbsp;Cristina Paules ,&nbsp;Daniel Oros ,&nbsp;Jon Schoorlemmer","doi":"10.1016/j.placenta.2025.02.018","DOIUrl":"10.1016/j.placenta.2025.02.018","url":null,"abstract":"<div><h3>Introduction</h3><div>During initial stages of the pandemic, SARS-CoV-2 infection during pregnancy was related to adverse pregnancy outcomes and alterations in the placenta. Whether placental abnormalities in pregnant women with COVID-19 still persist afterwards remains poorly studied. Here, we determined whether the absence of obstetric complications after maternal COVID-19 disease, including preeclampsia, is accompanied by a complete return to normalcy in terms of placental physiology.</div></div><div><h3>Methods</h3><div>Placental RNA was purified from placental samples from SARS-CoV-2 positive mothers taken either in 2022, when Omicron was the predominant variant of concern (termed Omicron) (n = 21); or from healthy pregnancies predating the pandemic (termed preCOVID-19). Our cohort included samples from pregnant women who got infected weeks and even months before term. We performed RNA-seq, identified differentially expressed genes and examined to which biological, biochemical and cellular pathways they belong, using gene set enrichment analysis.</div></div><div><h3>Results</h3><div>We identified 71 differentially expressed genes (DEGs) (defined by p-value ≤0.05 and fold change (FC) of ≤ -2 or ≥2). The alterations identified in placentas delivered by mothers who suffered an episode of COVID-19 disease could be mainly attributed to pathways related to organogenesis, extracellular matrix organization and oxygen transport. These alterations were also detected after exclusion of gestational diabetes mellitus (GDM) samples. Although none of the samples were taken from cases of preeclampsia, several of the relevant DEGs have been previously reported as dysregulated in hypertensive disorders of pregnancy including preeclampsia.</div></div><div><h3>Discussion</h3><div>We propose that maternal SARS-CoV-2 infection causes alterations in gene expression that are indicative of vascular defects in the placenta.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"165 ","pages":"Pages 127-135"},"PeriodicalIF":3.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143852320","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":"Maternal background and perinatal complications in MCI: A retrospective cohort study","authors":"Tatsuya Yoshihara,&nbsp;Yasuhiko Okuda,&nbsp;So Owada,&nbsp;Yosuke Ono,&nbsp;Satoko Sasatsu,&nbsp;Maki Ogi,&nbsp;Eriko Ogasahara,&nbsp;Osamu Yoshino","doi":"10.1016/j.placenta.2025.02.017","DOIUrl":"10.1016/j.placenta.2025.02.017","url":null,"abstract":"<div><h3>Objective</h3><div>Marginal cord insertion (MCI) is often defined as an abnormal placental cord insertion (PCI), yet there is limited discussion on the maternal backgrounds and perinatal complications associated with its occurrence. This retrospective cohort study aimed to investigate maternal backgrounds associated with MCI and to compare perinatal outcomes between MCI and normal PCI.</div></div><div><h3>Materials and methods</h3><div>The study included 1038 deliveries from 2021 to 2023 in our institution, examining maternal backgrounds and perinatal outcomes. Multivariable logistic regression analysis was conducted for variables that showed significance in univariate analysis of maternal backgrounds. For perinatal outcomes, variables that exhibited significance were further analyzed using multivariable logistic regression, considering factors previously reported to be associated with those events.</div></div><div><h3>Results</h3><div>9.5 % exhibited MCI. Assisted reproductive technology, nulliparous, and congenital uterine anomalies were identified as independent risk factors for MCI. In perinatal outcomes, fetal growth restriction (FGR) and emergency cesarean section were significantly more prevalent in cases with MCI. Even when compared to factors previously reported to be associated with FGR and emergency cesarean section, MCI remained an independent risk factor.</div></div><div><h3>Conclusion</h3><div>In addition to previously reported factors such as ART and primiparity, uterine anomalies were also identified as risk factors for MCI. It is important to manage MCI with the awareness that it increases the incidence of perinatal complications.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"163 ","pages":"Pages 29-32"},"PeriodicalIF":3.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526910","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":"Vaginal miR-210-3p as a potential biomarker for pregnancies complicated by early fetal growth restriction: A proof-of-concept case-control study","authors":"Elisabetta Bigagli ,&nbsp;Elisa Spataro ,&nbsp;Lucia Pasquini ,&nbsp;Lorenzo Cinci ,&nbsp;Mario D'Ambrosio ,&nbsp;Chiara De Blasi ,&nbsp;Chiara Bartolini ,&nbsp;Felice Petraglia ,&nbsp;Cristina Luceri","doi":"10.1016/j.placenta.2025.02.015","DOIUrl":"10.1016/j.placenta.2025.02.015","url":null,"abstract":"<div><h3>Introduction</h3><div>Fetal growth restriction (FGR) is associated with increased risk of neonatal morbidity and mortality or long-term adverse outcomes. We investigated the ability of hypoxia and angiogenesis-related miR-210-3p and miR-126-5p to identify early FGR cases and their correlations with neonatal outcomes.</div></div><div><h3>Methods</h3><div>Twenty-nine women with pregnancies complicated by early FGR diagnosis and 25 controls matched for gestational age (GA) were enrolled and their vaginal fluid (VF) and plasma were collected. MiR-210-3p and miR-126-5p were measured by RT-qPCR and their targets were identified by in-silico analysis limited only to those already experimentally validated in other contexts.</div></div><div><h3>Results</h3><div>Overall, VF levels of miR-210-3p were lower in early FGR cases compared to controls (p &lt; 0.05). miR-210-3p was lower in severe cases and in women who later developed preeclampsia (p &lt; 0.05). VF miR-210-3p levels correlated with lower birth weight, premature birth and severe complications at birth (p &lt; 0.05). miR-210-3p was not detected in plasma and no correlations were observed between miR-126-5p and FGR or neonatal outcomes. In silico analyses identified HIF-1α, HIF-3α, BDNF, IGFBP3, RAD52 and TWIST-1 as experimentally validated targets of miR-210-3p. Among the predicted biological pathways controlled by miR-210-3p, we found hypoxia-responsive signaling such as autophagy, oxidative stress and metabolic pathways.</div></div><div><h3>Discussion</h3><div>Although validation is needed, these findings suggest that VF levels of miR-210-3p may potentially serve as biomarker for the diagnosis of early FGR; future mechanistic studies are also advisable to investigate whether pharmacological strategies based on miR-210-3p, or its downstream targets may be useful for FGR.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"163 ","pages":"Pages 8-15"},"PeriodicalIF":3.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512092","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":"In vitro differentiation of macaque extravillous trophoblasts in a low oxygen environment","authors":"Logan T. Keding ,&nbsp;Avery R. Heselton ,&nbsp;Emily Ren ,&nbsp;Sarah A. Shaw ,&nbsp;Michelle R. Koenig ,&nbsp;Thaddeus G. Golos ,&nbsp;Jenna K. Schmidt","doi":"10.1016/j.placenta.2025.02.014","DOIUrl":"10.1016/j.placenta.2025.02.014","url":null,"abstract":"<div><h3>Introduction</h3><div>Early primate placental development occurs within a low oxygen (O₂) environment, whereas <em>in vitro</em> differentiation of trophoblasts is performed at supraphysiologic O₂ levels. Macaque trophoblast stem cells (TSCs) are capable of differentiation to extravillous trophoblasts (EVTs) <em>in vitro</em>, yet the morphological heterogeneity observed across cells lines necessitates evaluation of optimal culture conditions. Our objectives were to determine the impact of oxygen on the <em>in vitro</em> differentiation of macaque TSCs and to refine the molecular characterization of TSC-differentiated EVTs.</div></div><div><h3>Methods</h3><div>Macaque TSCs were differentiated to EVTs in either 20% or 5% O₂. Gene and protein expression profiles were compared between TSCs and EVTs and between differentiation conditions. Immunohistochemical analysis was performed on early gestation macaque placental tissues to assess <em>in vivo</em> expression of Ki-67, NCAM1 and monkey chorionic gonadotropin (mCG).</div></div><div><h3>Results</h3><div>EVTs differentiated in 20% O₂ had significantly higher expression of <em>CGA</em>, <em>CGB</em> and <em>NOTCH2</em> and decreased <em>HIF1A</em> expression compared to those cultured in 5% O₂. Regardless of oxygen condition, nearly all EVTs expressed NCAM1 and Mamu-AG, the macaque-specific homolog of human EVT marker HLA-G. <em>In vivo</em> placental expression of NCAM1 was restricted to EVTs within the trophoblastic shell and endovasculature, revealing a macaque EVT marker within the placenta.</div></div><div><h3>Discussion</h3><div>Reduced oxygen minimally impacted macaque EVT differentiation <em>in vitro</em>. Elevated expression of the endovascular EVT marker <em>NOTCH2</em> potentially suggests that 20% O₂ supported differentiation of more mature EVTs. Altogether, a standard 20% O₂ environment supports macaque EVT differentiation <em>in vitro</em> and the results further validate the identity of macaque TSC-differentiated EVTs.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"163 ","pages":"Pages 16-28"},"PeriodicalIF":3.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526909","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}