Placenta最新文献

{"title":"Gene expression profiles based on maternal plasma cfDNA nucleosome footprints indicate fetal development and maternal immunity changes during pregnancy progress","authors":"Min Zhang ,&nbsp;Kun Li ,&nbsp;Xiang Huang ,&nbsp;Huiling Zhou ,&nbsp;Jiayu Tan ,&nbsp;Zhiwei Guo ,&nbsp;Xingyu Wei ,&nbsp;Yuming Liu ,&nbsp;Shi Weng ,&nbsp;Guojun Ouyang ,&nbsp;Xuexi Yang ,&nbsp;Wenbo Hao ,&nbsp;Fenxia Li","doi":"10.1016/j.placenta.2024.12.005","DOIUrl":"10.1016/j.placenta.2024.12.005","url":null,"abstract":"<div><h3>Background</h3><div>Pregnancy significantly alters the maternal immune system, affecting fetal development. The collection of tissues from the human placenta and fetus is not ethically or practically feasible at various gestational stages, thus limiting the study of gene expression in the fetus and placenta. Recent studies have shown that plasma cell-free DNA (cfDNA) nucleosome patterns can predict gene expression in the source tissue, offering insights into an individual's health status. This study aimed to identify pregnancy-related gene expression changes across gestational periods using cfDNA nucleosome distribution to understand fetal development and maternal immune changes.</div></div><div><h3>Methods</h3><div>Plasma samples were collected from 150 healthy pregnant women in different trimesters (early, mid, and late) and 32 healthy nonpregnant women. The correlation between gene expression and physiological changes during pregnancy was evaluated by inferring differential expression profiles around the transcription start site (TSS) using cfDNA nucleosome distribution patterns obtained through whole-genome sequencing. We utilized Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to annotate differentially expressed genes with the mother and fetus.</div></div><div><h3>Results</h3><div>We identified gene expression changes that support the regulation of fetal development and immune system function during pregnancy. Differential coverage genes were mainly enriched in pathways related to transcription and translation, organic compound metabolism, and immune regulation. In addition, differentially expressed genes with significant temporal trends were identified. Among them, the upregulated differential genes were mainly related to development, whereas those with downregulated trends were mainly related to the immune system response. This indicates that differential changes of the placenta and maternal are significantly correlated with the pregnancy status.</div></div><div><h3>Discussion</h3><div>This study demonstrated the differential gene expression represented by the characteristic distribution of cfDNA nucleosome in maternal peripheral blood can effectively capture significant changes in maternal immunity and fetal development throughout pregnancy stages. It may help identify abnormal gene expression patterns associated with complications in pregnancy and childbirth, enhancing the quality of life and safety for both mother and fetus.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"159 ","pages":"Pages 84-92"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829862","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":"Profilin-1 levels in preeclampsia: Associations with disease and adverse neonatal outcomes","authors":"Sadullah Özkan ,&nbsp;Alperen Aksan ,&nbsp;Fahri B. Fıratlıgil ,&nbsp;Dilara Kurt ,&nbsp;Serap Sucu ,&nbsp;Aslıhan Coşkun ,&nbsp;Kadriye Yakut Yücel ,&nbsp;A. Turhan Çağlar ,&nbsp;Yaprak Engin Üstün","doi":"10.1016/j.placenta.2024.12.012","DOIUrl":"10.1016/j.placenta.2024.12.012","url":null,"abstract":"<div><h3>Background</h3><div>Preeclampsia is a serious pregnancy complication requiring early detection to improve outcomes. Profilin-1 (PFN1), linked to vascular dysfunction, may serve as a biomarker for diagnosing preeclampsia and predicting adverse neonatal outcomes. The aim of this study was to determine the serum Profilin-1 levels in patients diagnosed with preeclampsia and to investigate its association with disease severity and adverse neonatal outcomes.</div></div><div><h3>Methods</h3><div>A prospective cross-sectional study was conducted at Etlik City Hospital involving 40 women with preeclampsia and 40 healthy controls. Serum PFN1 levels were measured by ELISA and results were compared between groups. The results were compared between the groups. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of PFN1.</div></div><div><h3>Results</h3><div>Serum PFN1 levels were significantly higher in the preeclampsia group compared to controls (46.48 [30.23–60.29] vs. 26.41 [19.65–41.76], p &lt; 0.001). The ROC curve showed good diagnostic accuracy for PFN1 in detecting preeclampsia with an AUC of 0.741 (95 % CI: 0.631–0.832, p &lt; 0.001), a sensitivity of 95 % and a specificity of 42.5 %. PFN1 levels were also associated with composite neonatal outcomes, with an AUC of 0.622 (95 % CI: 0.520–0.716, p = 0.042).</div></div><div><h3>Discussion</h3><div>PFN1 is a potential biomarker for the diagnosis of preeclampsia. However, further studies are needed to validate its role in predicting adverse neonatal outcomes and to improve its specificity for clinical use.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"159 ","pages":"Pages 140-145"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896799","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":"A transcriptomic comparison of in vitro models of the human placenta","authors":"Samantha Lapehn ,&nbsp;Sidharth Nair ,&nbsp;Evan J. Firsick ,&nbsp;James MacDonald ,&nbsp;Ciara Thoreson ,&nbsp;James A. Litch ,&nbsp;Nicole R. Bush ,&nbsp;Leena Kadam ,&nbsp;Sylvie Girard ,&nbsp;Leslie Myatt ,&nbsp;Bhagwat Prasad ,&nbsp;Sheela Sathyanarayana ,&nbsp;Alison G. Paquette","doi":"10.1016/j.placenta.2024.11.007","DOIUrl":"10.1016/j.placenta.2024.11.007","url":null,"abstract":"<div><h3>Introduction</h3><div>Selecting an in vitro culture model of the human placenta is challenging due to representation of different trophoblast cell types with distinct biological roles and limited comparative studies that define key characteristics of these models. The aim of this research was to compare the transcriptomes of common in vitro models of the human placenta compared to bulk human placental tissue.</div></div><div><h3>Methods</h3><div>We performed differential gene expression analysis on publicly available transcriptomic data from 7 in vitro models of the human placenta (HTR-8/SVneo, BeWo, JEG-3, JAR, Primary Trophoblasts, Villous Explants, and Trophoblast Stem Cells) and compared to bulk placental tissue from 2 cohort studies (CANDLE and GAPPS) or individual trophoblast cell types derived from bulk placental tissue.</div></div><div><h3>Results</h3><div>All in vitro placental models had a substantial number of differentially expressed genes (DEGs, FDR&lt;0.01) compared to the CANDLE and GAPPS placentas (Average DEGs = 10,624), and the individual trophoblast cell types (Average DEGs = 5413), indicating that there are vast differences in gene expression. Hierarchical clustering identified 54 gene clusters with distinct expression profiles across placental models, with 23 clusters enriched for specific KEGG pathways. Placental cell lines were classified by fetal sex based on expression of Y-chromosome genes that identified HTR-8/SVneo cells as female origin, while JEG-3, JAR, and BeWo cells are of male origin.</div></div><div><h3>Discussion</h3><div>None of the models were a close approximation of the human bulk placental transcriptome, highlighting the challenges with model selection. To enable appropriate model selection, we adapted our data into a web application: “Comparative Transcriptomic Placental Model Atlas (CTPMA)”.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"159 ","pages":"Pages 52-61"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786513","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":"Sexual dimorphism in lipidomic changes in maternal blood and placenta associated with obesity and gestational diabetes: A discovery study","authors":"Leena Kadam ,&nbsp;Marija Veličković ,&nbsp;Kelly Stratton ,&nbsp;Carrie D. Nicora ,&nbsp;Jennifer E. Kyle ,&nbsp;Eric Wang ,&nbsp;Matthew E. Monroe ,&nbsp;Lisa M. Bramer ,&nbsp;Leslie Myatt ,&nbsp;Kristin E. Burnum-Johnson","doi":"10.1016/j.placenta.2024.12.002","DOIUrl":"10.1016/j.placenta.2024.12.002","url":null,"abstract":"<div><h3>Introduction</h3><div>The placenta uses lipids and other nutrients to support its own metabolism hence impacting the type and amount of these substrates available to the growing fetus. Maternal obesity and gestational diabetes (GDM) can disrupt placental lipid metabolism and thus lead to altered fetal growth contributing to adverse pregnancy outcomes and developmentally programing the offspring for disease in later life. Understanding obesity and GDM driven changes in placental lipid metabolism is thus important.</div></div><div><h3>Methods</h3><div>We collected maternal plasma and placental villous tissue following elective cesarean section at term from women who were lean (pre-pregnancy BMI 18.5–24.9), obese (BMI&gt;30) or obese with type A2 GDM n = 8 each group (4 male and 4 female placentas). Fatty acid composition of different lipid classes was analyzed by LC-MS/MS analysis. Significant changes in GDM vs obese, GDM vs lean, and obese vs lean were determined in both a fetal sex-dependent and independent manner.</div></div><div><h3>Results</h3><div>In placenta 436 lipids were identified, among which 85 showed significant changes. We report significant changes in placental triglyceride, phosphatidylcholine, and phosphatidylinositol lipids containing essential fatty acids- DHA and AA in GDM, with male placentas driving these changes. In maternal plasma, 284 lipids were identified with 14 showing significant changes, but we observed no changes based on fetal sex.</div></div><div><h3>Discussion</h3><div>Maternal obesity and GDM impact placental lipid composition in a sexually dimorphic manner. The alteration in specific lipid classes can impact cellular energetics and placental function.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"159 ","pages":"Pages 76-83"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813996","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 role of the intraplacental fetal artery in predicting the need for cesarean-hysterectomy in women at high risk for placenta accreta spectrum","authors":"Murat Levent Dereli ,&nbsp;Sadun Sucu ,&nbsp;Serap Topkara Sucu ,&nbsp;Sadullah Özkan ,&nbsp;Fahri Burçin Fıratlıgil ,&nbsp;Kadriye Yakut Yücel ,&nbsp;Firdevs Şahin Duran ,&nbsp;Yaprak Engin Üstün ,&nbsp;Şevki Çelen ,&nbsp;Ali Turhan Çağlar","doi":"10.1016/j.placenta.2024.12.013","DOIUrl":"10.1016/j.placenta.2024.12.013","url":null,"abstract":"<div><h3>Introduction</h3><div>Prenatal determination of placenta accreta spectrum (PAS) and its severity is crucial, as it is a highly morbid condition. The aim was to investigate the intraplacental fetal artery (IFA) as a novel ultrasonographic marker in predicting cesarean-hysterectomy need in PAS.</div></div><div><h3>Methods</h3><div>A prospective observational cohort study was conducted with a total of 62 women with placenta previa and ≥1 previous cesarean-section who were managed for PAS between September 2022 and January 2024. All women were classified according to the ultrasonographic classification system for prenatal PAS, and ultrasonographic assessments for IFA were performed. Odds ratios were calculated to test the association of IFA and other parameters related to PAS with cesarean-hysterectomy need. Receiver operating characteristic analysis was performed to evaluate the ability of maximum diameter (D-max) of IFA to predict cesarean-hysterectomy need.</div></div><div><h3>Results</h3><div>The study was completed with 49 women who underwent a cesarean-section with uterus-sparing surgery (n = 22) and a cesarean-hysterectomy (n = 27). Outer placental-half extension of IFA and each 1 mm increase in IFA D-max &gt;3.5 mm were associated with a 58.82- and 3.52-fold increased risk of cesarean-hysterectomy, respectively. An IFA D-max of &gt;3.5 mm was associated with cesarean-hysterectomy need at any PAS stage [area under the curve (AUC) = 0.845, 95 % CI:0.71–0.93, p &lt; 0.001)] and in PAS 2 patients (AUC = 0.750, 95 % CI:0.56–0.89, p = 0.010), in whom prenatal prediction of cesarean-hysterectomy need is difficult.</div></div><div><h3>Discussion</h3><div>Evaluation of D-max and outer placental-half extension of IFA along with other markers of PAS improved the ability of ultrasonography to predict cesarean-hysterectomy need.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"159 ","pages":"Pages 154-160"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896929","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-nuclei RNA-sequencing fails to detect molecular dysregulation in the preeclamptic placenta","authors":"Inbal Admati ,&nbsp;Niv Skarbianskis ,&nbsp;Hannah Hochgerner ,&nbsp;Osnat Ophir ,&nbsp;Simcha Yagel ,&nbsp;Ido Solt ,&nbsp;Amit Zeisel","doi":"10.1016/j.placenta.2024.12.011","DOIUrl":"10.1016/j.placenta.2024.12.011","url":null,"abstract":"<div><h3>Introduction</h3><div>Single-cell RNA-seq (scRNA-seq) revolutionized our understanding of tissue complexity in health and disease and revealed massive transcriptional dysregulation across placental cell classes in early-onset, but not late-onset preeclampsia (PE). However, the multinucleated syncytium is largely inaccessible to cell dissociation. Nuclei isolation and single-nuclei RNA-seq may be preferable in the placenta; not least considering compatibility with long-term tissue storage. Yet, nuclei contain a subsample of the cells’ transcriptional profile. Mature transcripts critical to cellular function and disease may be missed.</div></div><div><h3>Methods</h3><div>We analyzed placenta from pregnancies using single-cell and single-nuclei RNA-seq. The datasets comprise 45,836 cells and 27,078 nuclei, from 10 to 7 early-onset preeclampsia (EPE) cases and 3 and 2 early idiopathic controls (ECT), respectively. We compared the methods’ sensitivities, cell type detection, differential gene expression in PE, and performed histological validations.</div></div><div><h3>Results</h3><div>Mature syncytiotrophoblast were sampled ∼50x more efficiently after nuclei extraction. Yet, scRNA-seq was more sensitive in detection of genes, molecules and mature transcripts. In snRNA-seq, nuclei of all placental cell classes suffered ambient trophoblast contamination. Transcripts from extravillous trophoblast, stroma, vasculature and immune cells were profiled less comprehensively by single-nuclei RNA-seq (snRNA-seq), restricting cell-type detection. In EPE, we found dysregulation of angiogenic actors <em>FLT1</em>/<em>PGF</em> both in prefused syncytiotrophoblast after cell extraction, and mature syncytiotrophoblast after nuclei isolation. Disease-related stress and inflammation were undetected from nuclei.</div></div><div><h3>Discussion</h3><div>scRNA-seq has important advantages over snRNA-seq for comprehensive transcriptomics studies of the placenta, especially to understand cell-type resolved dysregulation in pathologies. Yet, to address the dilemma of an underrepresented syncytium, studies benefit from complementary nuclei extraction.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"159 ","pages":"Pages 170-179"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903474","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":"Relationship between serum levels of ANGPTL8, Apo C2, and human placental lactogen (hPL) in patients with gestational diabetes mellitus: Interaction of LPL regulators with hPL, a possible contributing factor to insulin resistance","authors":"Emre Ispir ,&nbsp;Ercan Saruhan ,&nbsp;Deniz Ilhan Topcu ,&nbsp;Bugra Varol ,&nbsp;Eren Akbaba ,&nbsp;Tuba Cakmak","doi":"10.1016/j.placenta.2024.12.007","DOIUrl":"10.1016/j.placenta.2024.12.007","url":null,"abstract":"<div><h3>Introduction</h3><div>Gestational diabetes mellitus (GDM) is defined as glucose intolerance during pregnancy. We aimed to investigate the potential effects of betatrophin and ApoC2 in GDM, focusing on their roles in LPL (lipoprotein lipase) regulation and their relationship with hPL to elucidate the possible impact of hPL on lipid metabolism and its potential contribution to the development of GDM.</div></div><div><h3>Methods</h3><div>Thirty pregnant women with normal glucose tolerance and 29 with gestational diabetes mellitus (diagnosed by 75g OGTT between 24 and 28 weeks) were included in the study. Serum betatrophin, hPL, and ApoC2 were measured by Elisa and HOMA-IR was calculated.</div></div><div><h3>Results</h3><div>In the GDM group, hPL levels correlated with betatrophin and ApoC2 (r = 0.552, p &lt; 0.05; r = 0.588, p &lt; 0.05 respectively) while betatrophin correlated with the ApoC2 (r = 0.584, p &lt; 0.05). A linear relationship between hPL and betatropin and also between hPL and ApoC2 values in the control group (r = 0.454, p &lt; 0.05; r = 0.779, p &lt; 0.01 respectively) were observed. ApoC2 levels in the GDM group (n = 20) with HOMA-IR cut-off &gt;2.5 were significantly higher than the control group (n = 10) (p &lt; 0.05). There was also a positive relationship between betatrophin and ApoC2 (r = 0.591) (p &lt; 0.05).</div></div><div><h3>Discussion</h3><div>GDM patients may have impaired LPL enzyme regulation in addition to insulin resistance, with hPL potentially contributing to this disruption. Impaired lipoprotein lipase activity and its dysregulation secondary to genetic disorders may play a role in the etiopathogenesis of GDM. Further investigation into the correlation between betatrophin, ApoC2, and other LPL modulators in patients with various forms of diabetes could be beneficial for understanding this interaction more comprehensively.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"159 ","pages":"Pages 119-125"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of SARS-CoV-2 Infection during pregnancy with placental weight and histopathologic lesions","authors":"Regan N. Theiler ,&nbsp;Simrit K. Warring ,&nbsp;Maia C. Young ,&nbsp;Janelle Santos ,&nbsp;Megan E. Branda ,&nbsp;Reade A. Quinton ,&nbsp;Elizabeth Ann L. Enninga","doi":"10.1016/j.placenta.2024.12.017","DOIUrl":"10.1016/j.placenta.2024.12.017","url":null,"abstract":"<div><h3>Introduction</h3><div>The reported gross and histopathologic changes in the placenta associated with SARS-CoV-2 infection are heterogeneous. We sought to summarize placental histopathologic findings from pregnancies affected by SARS-CoV-2 infection according to timing of infection and symptom severity.</div></div><div><h3>Methods</h3><div>We conducted a retrospective cohort study of patients with SARS-CoV-2 infection during pregnancy who had deliveries at Mayo Clinic, Rochester, Minnesota, from April 2020 through June 2021. Placental histopathologic findings and clinical characteristics were compared for infections before vs after 28 weeks’ gestation and according to COVID-19 symptom severity.</div></div><div><h3>Results</h3><div>We analyzed 93 cases of SARS-CoV-2 infection during pregnancy, with 51 % of infections occurring before 28 weeks' gestation. Infections were categorized as asymptomatic (14 %), mild (77 %), moderate (6 %), and severe (3 %) according to World Health Organization criteria. An increased risk of small placental weight (&lt;10th percentile) was associated with maternal infection at all gestational ages (30 %, <em>P</em> &lt; .001). Histopathologic lesions consistent with maternal vascular malperfusion occurred more often for infections before than after 28 weeks’ gestation (18/46, 38 % vs 9/47, 19 %; <em>P</em> = .047) and did not differ in frequency according to symptom severity. Inflammatory changes were present in 50 % of the placentas examined but did not differ by group, except that acute fetal vasculitis occurred more frequently after asymptomatic vs symptomatic maternal infection (23 % vs 5 %; risk ratio, 4.62; 95 % CI, 1.16–18.30).</div></div><div><h3>Discussion</h3><div>COVID-19 at any gestational age or severity increases the risk of small placental weight and the presence of placental inflammatory lesions.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"159 ","pages":"Pages 180-186"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907479","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":"Effects of sildenafil treatment on placental immune cell subsets in early-onset fetal growth restriction","authors":"R.E. Bezemer ,&nbsp;J.E. Brenøe ,&nbsp;M.H. Schoots ,&nbsp;M.E. Feenstra ,&nbsp;H. van Goor ,&nbsp;W. Ganzevoort ,&nbsp;S.J. Gordijn ,&nbsp;J.R. Prins","doi":"10.1016/j.placenta.2024.11.014","DOIUrl":"10.1016/j.placenta.2024.11.014","url":null,"abstract":"<div><h3>Introduction</h3><div>Early onset fetal growth restriction is a common pregnancy complication with significant risk of perinatal mortality and morbidity. The most common etiology is placental insufficiency, reflected by several placental lesions that appear with fetal growth restriction. Placental immune cells are involved in almost all aspects of the development of the placenta and immune cell imbalances have been related to common pregnancy complications. The STRIDER trial investigated the therapeutic potential of sildenafil. No clinical improvements were observed, however, since sildenafil can have immunological effects, we aimed to investigate if sildenafil alters local placental immune cells.</div></div><div><h3>Methods</h3><div>Placental samples from 146 patients were included from the STRIDER trial and stained with IHC for leukocytes (CD45), macrophages (CD68 and CD206), T cells (CD3 and CD8), regulatory T cells (FOXP3) and NK cells (CD56). Immune cells were quantified in the decidua basalis and villi at term using a trained detection classifier. In addition, maternal plasma cytokines were measured at inclusion.</div></div><div><h3>Results</h3><div>In the sildenafil group, numbers of CD3⁺ T cells, CD68⁺ and CD206⁺ macrophages and CD56⁺ NK cell were greater in the decidua basalis compared to the control group. Correlating maternal plasma cytokines to placental immune cell subsets showed predominantly negative correlations in the placebo group, whereas most cytokines correlated positively to placental immune cells in the sildenafil group.</div></div><div><h3>Discussion</h3><div>Our data demonstrates the immunomodulatory effects of sildenafil in pregnancies complicated by early onset fetal growth restriction and offers valuable insights on the use of immunomodulatory drugs in pregnancy.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"159 ","pages":"Pages 62-69"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792348","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":"Immunosuppressant drug tacrolimus inhibits HUVEC angiogenesis and production of placental growth factor","authors":"Jennifer H. Yo ,&nbsp;Kirsten R. Palmer ,&nbsp;David Nikolic-Paterson ,&nbsp;Peter G. Kerr ,&nbsp;Sarah A. Marshall","doi":"10.1016/j.placenta.2024.12.010","DOIUrl":"10.1016/j.placenta.2024.12.010","url":null,"abstract":"<div><h3>Background</h3><div>Tacrolimus is a cornerstone of immunosuppression in solid organ transplants, but its use is linked with the development of endothelial dysfunction. Pregnant solid organ transplant recipients are four to six times more likely to develop preeclampsia, which is also associated with endothelial dysfunction. Therefore, this <em>in vitro</em> study investigated the acute effects of tacrolimus on the expression of common angiogenic factors related to preeclampsia, and effects on angiogeneis in primary human tissues.</div></div><div><h3>Methods</h3><div>Primary human umbilical vein endothelial cells (HUVECs) were exposed to tacrolimus (0, 5, 20, 50 ng/mL) for 24h alone, or in combination with tumour necrosis factor (TNF, 10 ng/mL) and high dose glucose (25 mM). Cell culture concentrations of sFlt-1, PlGF and activin A were measured. In addition, the effect of tacrolimus on markers of endothelial dysfunction and permeability were assessed, as were the effect of tacrolimus on tube formation. Angiogenic factors and mRNA markers of oxidative stress and inflammation were also assessed in primary placental tissue after an acute 24 h exposure to tacrolimus.</div></div><div><h3>Results</h3><div>Tacrolimus exposure significantly reduced HUVEC secretion of PlGF, increased production of activin A, andreduced tubular structure formation without impacting cell permeability or viability. There was no change in ICAM1 or VCAM1 expression in HUVECs treated with tacrolimus treatment alone, however co-culture with TNF significantly increased expression of ICAM1 and VCAM1. In placental explants tacrolimus did not change angiogenic factor production or markers of inflammation or oxidative stress.</div></div><div><h3>Conclusion</h3><div>An acute tacrolimus exposure reduced PlGF secretion and impaired angiogenesis in primary endothelial cells, without affecting. These findings provide a potential mechanistic basis for tacrolimus to contribute to the endothelial dysfunction contributing to preeclampsia.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"159 ","pages":"Pages 146-153"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896781","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}