PlacentaPub Date : 2025-01-01DOI: 10.1016/j.placenta.2024.11.014
R.E. Bezemer , J.E. Brenøe , M.H. Schoots , M.E. Feenstra , H. van Goor , W. Ganzevoort , S.J. Gordijn , J.R. Prins
{"title":"Effects of sildenafil treatment on placental immune cell subsets in early-onset fetal growth restriction","authors":"R.E. Bezemer , J.E. Brenøe , M.H. Schoots , M.E. Feenstra , H. van Goor , W. Ganzevoort , S.J. Gordijn , 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<sup>+</sup> T cells, CD68<sup>+</sup> and CD206<sup>+</sup> macrophages and CD56<sup>+</sup> 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}
PlacentaPub Date : 2025-01-01DOI: 10.1016/j.placenta.2024.12.010
Jennifer H. Yo , Kirsten R. Palmer , David Nikolic-Paterson , Peter G. Kerr , Sarah A. Marshall
{"title":"Immunosuppressant drug tacrolimus inhibits HUVEC angiogenesis and production of placental growth factor","authors":"Jennifer H. Yo , Kirsten R. Palmer , David Nikolic-Paterson , Peter G. Kerr , 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}
PlacentaPub Date : 2025-01-01DOI: 10.1016/j.placenta.2024.12.009
Leticia T. Casarotto , Helen N. Jones , Pascale Chavatte-Palmer , Geoffrey E. Dahl
{"title":"Late gestation heat stress alters O2 regulation in placenta and neonatal heifers","authors":"Leticia T. Casarotto , Helen N. Jones , Pascale Chavatte-Palmer , Geoffrey E. Dahl","doi":"10.1016/j.placenta.2024.12.009","DOIUrl":"10.1016/j.placenta.2024.12.009","url":null,"abstract":"<div><h3>Introduction</h3><div>Maternal hyperthermia (i.e. heat stress) can adversely affect placental development and function, with severity varying based on pregnancy stage. During the last half of pregnancy, cow uterine blood flow increases 4.5-fold, and decreased maternal blood circulation can reduce placental diffusion capacity, impacting fetal growth.</div></div><div><h3>Material and methods</h3><div>Milk removal was discontinued (i.e. dried off) in multiparous pregnant Holstein cows 54 ± 5 days before expected calving and assigned to cooling (CLD) or heat stress (HT) treatments. Oxygen measurements were taken within ±3 h after birth (n = 7 per group) using the Rad-G Pulse Oximeter. RNA sequencing of cotyledonary tissue examined pathways and genes related to gas and oxygen transport.</div></div><div><h3>Results</h3><div>Heifers exposed to late gestation <em>in utero</em> hypoxia (HT) had significantly lower oxygen saturation at birth compared with those from dams with normal (CLD) oxygen levels (83.4 % vs. 90.7 %, p = 0.03). The peripheral index of oxygen diffusion was also lower in HT-exposed heifers (2.04 % vs. 4.84 %, p = 0.01). Gene enrichment analysis of cotyledonary tissue revealed affected pathways, including response to hypoxia, oxygen transport, and VEGF signaling. Late gestation HT potentially influenced blood circulation and nitric oxide biosynthesis pathways, with various genes showing upregulation and downregulation.</div></div><div><h3>Discussion</h3><div>The placenta is vital for fetal development, and late gestation hyperthermia can significantly affect its function, reducing fetal oxygen delivery and altering genes regulating placental gas and oxygen transport. These disruptions may result in fetal hypoxemia and growth restriction.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"159 ","pages":"Pages 126-130"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872645","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}
PlacentaPub Date : 2025-01-01DOI: 10.1016/j.placenta.2024.12.008
Hamdan Z. Hamdan
{"title":"Exploring gene expression signatures in preeclampsia and identifying hub genes through bioinformatic analysis","authors":"Hamdan Z. Hamdan","doi":"10.1016/j.placenta.2024.12.008","DOIUrl":"10.1016/j.placenta.2024.12.008","url":null,"abstract":"<div><h3>Introduction</h3><div>Preeclampsia (PE) is a multisystem disease that affects women during the pregnancy. Its pathogenicity remains unclear, and no definitive screening test can predict its occurrence so far. The aim of this study is to identify the critical genes that are involved in the pathogenicity of PE by applying integrated bioinformatic methods and to investigate the genes' diagnostic capability.</div></div><div><h3>Methods</h3><div>Datasets that investigated PE have been downloaded from Gene Expression Omnibus (GEO) datasets. Differential gene expression, weighted gene co-expression analysis (WGCNA), protein–protein interaction (PPI) network construction, and finally, the calculation of area under the curve and Receiver operating characteristic curve (ROC) analysis were done for the potential hub genes. The results generated from the GSE186257 dataset (discovery cohort) were validated in the GSE75010 dataset (validation cohort). Following validation of the hub-genes, a multilayer regulatory network was constructed to include the up-stream regulatory elements (transcription factors and miRNAs) of the validated hub-genes.</div></div><div><h3>Results</h3><div>WGCNA revealed six modules that were significantly correlated with PE. A total of 231 differentially expressed genes (DEGs) were identified. DEGs were intersected with the WGCNA modules' genes, totalling 55 genes. These shared genes were used to construct the PPI network; subsequently, four genes, namely FLT1, HTRA4, LEP and PAPPA2, were identified as hub-genes for PE in the discovery cohort. The expressional of these four hub genes were validated in the validation cohort and found to be highly expressed. ROC analysis in both datasets revealed that all these genes had a significant PE diagnostic ability. The regulatory network showed that FLT1 gene is the most connected and regulated gene among the validated hub-genes.</div></div><div><h3>Discussion</h3><div>This integrated analysis revealed that FLT1, LEP, HTRA4 and PAPPA2 may be strongly involved in the pathogenicity of PE and act as promising biomarkers and potential therapeutic targets for PE.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"159 ","pages":"Pages 93-106"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829860","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}
PlacentaPub Date : 2025-01-01DOI: 10.1016/j.placenta.2024.12.001
Ömer Demir , Miraç Özalp , Hüseyin Yaman , Fatih Mehmet Fındık
{"title":"The role of maternal blood elabela levels in the prediction of placenta previa and accreta","authors":"Ömer Demir , Miraç Özalp , Hüseyin Yaman , Fatih Mehmet Fındık","doi":"10.1016/j.placenta.2024.12.001","DOIUrl":"10.1016/j.placenta.2024.12.001","url":null,"abstract":"<div><h3>Introduction</h3><div>Placenta previa and Placenta Accreta Spectrum are life-threatening obstetric conditions that are challenging to diagnose accurately. Currently, there is no biochemical parameter available for their diagnosis. The aim of our study is to investigate the potential of Elabela as a laboratory marker that could predict placenta previa and placenta accreta, both of which can lead to severe, life-threatening complications for the mother.</div></div><div><h3>Methods</h3><div>In this study, which was conducted prospectively in two tertiary centers between 2020 and 2022, Elabela levels were examined in patient groups with placental insertion and invasion anomalies. SPSS program was used for comparative statistical analysis between groups.</div></div><div><h3>Results</h3><div>Of the 67 analyzed patients, 32 were in the control group, 12 were in the previa group, and 23 were in the accreta group. There was no statistically significant difference between the groups regarding age, BMI, number of curettages, presence of previous cesarean section, and smoking status. The Elabela level was measured at 135.6 ± 72.1 in the control group, 988.3 ± 925.5 in the previa group, and 376 ± 364.6 in the accreta group, with a statistically significant difference between the groups. The cut-off value of Elabela levels in the previa group was determined to be 304, with a sensitivity of 83.30 % and a specificity of 83.60 % (AUC = 0.909). In the accreta group, the cut-off value was 195.5, with a sensitivity of 60.90 % and a specificity of 61.40 % (AUC = 0.658).</div></div><div><h3>Discussion</h3><div>By showing that the prediction of placenta previa and placenta acreata can be made with a biochemical parameter in our study, young researchers will focus more on this subject and thus make many contributions to science.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"159 ","pages":"Pages 70-75"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794962","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}
PlacentaPub Date : 2025-01-01DOI: 10.1016/j.placenta.2024.12.016
R.I. Funwei , A. Olaleye , G.N. Uyaiabasi , W. Hammed , M.M. Obadimeji , C.J. Elikwu , A. Adepoju , C. Okangba , A. Akinyede , O. Ojurongbe , C. Falade , O. Walker
{"title":"Genetic profiling of Plasmodium falciparum antigenic biomarkers among asymptomatic pregnant women on intermittent preventive treatment with sulfadoxine-pyrimethamine from southwest Nigeria","authors":"R.I. Funwei , A. Olaleye , G.N. Uyaiabasi , W. Hammed , M.M. Obadimeji , C.J. Elikwu , A. Adepoju , C. Okangba , A. Akinyede , O. Ojurongbe , C. Falade , O. Walker","doi":"10.1016/j.placenta.2024.12.016","DOIUrl":"10.1016/j.placenta.2024.12.016","url":null,"abstract":"<div><h3>Introduction</h3><div>The genetic complexity of <em>Plasmodium falciparum</em> is contributory to the emergence of drug resistant-parasites. Intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) in malaria endemic settings is recommended by WHO. This study evaluated the prevalence of <em>Plasmodium falciparum multidrug resistance-1</em> gene (<em>Pfmdr</em>-1), genetic diversity of merozoite surface proteins (<em>msp-1</em>, <em>msp</em>-2) and glutamate-rich protein (<em>glurp</em>) among pregnant women with sub-patent parasitaemia from southwest Nigeria.</div></div><div><h3>Methods</h3><div>One hundred PCR-confirmed <em>Plasmodium falciparum</em> isolates, collected at first visit-V-1 (n = 52), delivery (n = 31) and cord blood (n = 17), were selected for analysis. The <em>Pfmdr</em>-1 alleles was evaluated using restriction fragment length polymorphism (RLFP), while <em>msp-1</em>, <em>msp-2</em> and <em>glurp</em> genes were genotyped. Allelic frequency distribution and multiplicity of infection were calculated at p-value ≤0.05.</div></div><div><h3>Results</h3><div>The <em>Pfmdr-1</em> (N86/N86Y) combination was detected in 11.8 %, 61.3 % and 58.8 % (p ≤ 0.05) in V-1, Delivery and Cord isolates respectively. The N86Y haplotype was detected only in cord (5.9 %). The allelic frequency distribution for <em>msp-1</em> was 244 (K1 = 81, MAD20 = 84 and RO33 = 79), and <em>msp-2;</em> 110 alleles, representing 43.6 % (FC27) and 56.4 % (3D7). While <em>glurp</em> expressed 25 alleles, 84 % (V-1), 12 % (delivery) and 4 % (cord), respectively (p ≤ 0.05). The <em>msp-1</em> and <em>msp-2</em> recorded higher MOIs than <em>glurp</em>.</div></div><div><h3>Discussion</h3><div>Genetically diverse <em>P. falciparum</em> strains with <em>Pfmdr-1</em> mutant alleles were detected in pregnant women with sub-patent parasitaemia in southwest Nigeria, which may reduce IPTp-SP effectiveness. Thus, continuous molecular surveillance of resistant-parasites to sulphadoxine-pyrimethamine and ACTs is essential.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"159 ","pages":"Pages 161-169"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896771","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}
PlacentaPub Date : 2025-01-01DOI: 10.1016/j.placenta.2024.12.006
Yurong Lu , Yijia Tian , Xiao Liu , Yongjie Tian , Xudong Zhao , Qinwen Li , Yuan Lu , Xietong Wang
{"title":"NETs exacerbate placental inflammation and injury through high mobility group protein B1 during preeclampsia","authors":"Yurong Lu , Yijia Tian , Xiao Liu , Yongjie Tian , Xudong Zhao , Qinwen Li , Yuan Lu , Xietong Wang","doi":"10.1016/j.placenta.2024.12.006","DOIUrl":"10.1016/j.placenta.2024.12.006","url":null,"abstract":"<div><h3>Background</h3><div>Inflammatory stress at the maternal-fetal interface plays an important role in the occurrence and development of preeclampsia(PE) caused by different etiologies. Many pathological neutrophil extracellular traps (NETs) at the maternal-fetal interface are believed to be among the main pathogenic factors leading to preeclampsia and the worsening of its symptoms. However, the underlying mechanism is largely unclear. This study aimed to elucidate the role of high mobility group box 1 (HMGB1) in NETs involved in the pathogenesis of PE.</div></div><div><h3>Methods</h3><div>The concentration of NETs was detected in the plasma of patients with PE using enzyme-linked immunosorbent assay (ELISA). Placental samples were collected from patients with PE to detect the expression of HMGB1 through Western Blot and PCR. For in vitro experiments, human trophoblast HTR-8/SVneo cells were treated with NETs, and their proliferation, invasion, migration, and apoptosis ability; degree of oxidative stress; and secretion of inflammatory factors were detected.</div></div><div><h3>Results</h3><div>Compared with that in normal pregnant women, an increase in the release of NETs was observed in the peripheral blood of patients with PE. HMGB1 was increased in the placenta of PE patients and colocalized with NETs. The treatment of human trophoblast HTR-8/SVneo cells with NETs resulted in the inhibition of HTR-8/SVneo cell invasion and migration and increases in the release of reactive oxygen species (ROS), and several inflammatory factors (IL-1β, IL-6, IL-8, and TNF-α). These damaging effects can be reversed by the HMGB1 scavenger glycyrrhizin, which indicates that NETs can mediate trophoblast damage and the expression of several inflammatory factors through HMGB1.</div></div><div><h3>Conclusion</h3><div>NETs can cause trophoblast inflammation-related functional damage through HMGB1 during the occurrence and development of preeclampsia. HMGB1 produces a marked effect in the PE cascade of oxidative stress involving NETs. Inhibiting HMGB1 to suppress NETs damage is a possible approach for the future treatment of PE.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"159 ","pages":"Pages 131-139"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882806","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}
PlacentaPub Date : 2024-12-28DOI: 10.1016/j.placenta.2024.12.014
Vinoth K Kothandan, Yingshi Ouyang, Elena Sadovsky, Alisa Komsky-Elbaz, Juliana S Powell, Jianping Xia, Tony J Huang, Yoel Sadovsky
{"title":"A multi-platform assessment of extracellular vesicles from the plasma and urine of women with preeclampsia.","authors":"Vinoth K Kothandan, Yingshi Ouyang, Elena Sadovsky, Alisa Komsky-Elbaz, Juliana S Powell, Jianping Xia, Tony J Huang, Yoel Sadovsky","doi":"10.1016/j.placenta.2024.12.014","DOIUrl":"10.1016/j.placenta.2024.12.014","url":null,"abstract":"<p><strong>Introduction: </strong>MicroRNAs (miRNAs), packaged within extracellular vesicles (EVs), have been used to interrogate the pathogenesis of preeclampsia and to identify its biomarkers. We have previously shown that miRNA species were differentially expressed in small plasma EVs from women with preeclampsia vs healthy controls. We sought to assess the use of rapid technologies for isolation of plasma and urine EVs from parturients with preeclampsia and determine differences in the expression of selected EV miRNA species.</p><p><strong>Methods: </strong>We collected blood and urine samples before delivery from parturients with severe preeclampsia vs healthy controls and used size exclusion chromatography (SEC) as an acceptable standard for rapid isolation of plasma EVs. We also isolated urine and plasma EVs using ExoDisc, a rapid nanofiltration technology for EV isolation. All samples were examined using a nanoparticle tracking analyzer, immunoblotting, and RT-qPCR for selected miRNA levels.</p><p><strong>Results: </strong>Whereas the concentration of EVs was higher in the urine from preeclampsia compared to controls, we observed the opposite change in plasma EVs, with no difference in EV size. Comparing the two patient groups for miRNA levels in EVs isolated by ExoDisc or SEC, we found that EV miR-93-5p was upregulated in the plasma and urine of parturients with preeclampsia vs healthy controls. Notably, miR-31-5p was upregulated in SEC- or ExoDisc-isolated plasma EVs, and miR-92-3p was upregulated in or ExoDisc-isolated plasma or urine EVs of parturients with preeclampsia.</p><p><strong>Discussion: </strong>Technologies for rapid analysis of plasma and urine EVs and their miRNA cargo provide complementary information that might be useful for deciphering pathways leading to preeclampsia and biomarkers for this disease.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922518","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}
PlacentaPub Date : 2024-12-05DOI: 10.1016/j.placenta.2024.12.003
Cherry Sun, Lawrence W Chamley, Joanna L James
{"title":"Organoid generation from trophoblast stem cells highlights distinct roles for cytotrophoblasts and stem cells in organoid formation and expansion.","authors":"Cherry Sun, Lawrence W Chamley, Joanna L James","doi":"10.1016/j.placenta.2024.12.003","DOIUrl":"https://doi.org/10.1016/j.placenta.2024.12.003","url":null,"abstract":"<p><strong>Background: </strong>Organoids are stem-cell derived, self-organised, three-dimensional cultures that improve in vitro recapitulation of tissue structure. The generation of trophoblast organoids using primary placental villous digests (containing cytotrophoblasts and trophoblast stem cells (TSC)) improved high-throughput assessment of early trophoblast differentiation. However, the relative contributions of cytotrophoblasts and TSCs to trophoblast organoid growth and differentiation remain unclear, with implications for model interpretation. Here we sought to generate organoids from side-population trophoblasts (SpTSCs) to better understand the contribution of TSC to trophoblast organoid formation.</p><p><strong>Methods: </strong>Methods were adapted from Haider et al., 2018 to generate organoids from Okae TSCs (OkTSCs) or SpTSCs. Organoid growth was compared with primary villous trophoblast organoids and cellular composition interrogated by immunohistochemistry.</p><p><strong>Results: </strong>Organoids can be derived from first-trimester SpTSCs that exhibit similar architecture to those from primary villous trophoblast. However, organoids established from pure TSC populations (OkTSC or SpTSC) have different growth dynamics to primary placental villous digest-derived organoids - with OkTSCs developing faster and spontaneously generating migratory cells, whilst SpTSC organoids grow more slowly. Importantly, depletion of SpTSC from first-trimester villous digests ablates organoid formation. Finally, the capacity of the side-population technique to isolate late-gestation TSC enabled the generation of trophoblast organoids from term placentae, although these were significantly smaller than their first-trimester SpTSC counterparts.</p><p><strong>Discussion: </strong>Together, this work highlights the requirement of TSC for organoid formation, and the functional distinction between TSC and cytotrophoblasts. Proof-of-principle data demonstrating organoid generation from late gestation TSC isolated directly from the placenta lays the groundwork for future disease models.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807314","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 pathology of IVF-conceived dichorionic diamniotic twins after fresh embryo versus frozen-thawed transfer","authors":"Ekaterina Shlush , Talal Sarhan , Rudi Hammudi , Ala Aiob , Alejandro Livoff , Susana Mustafa Mikhail , Lior Lowenstein , Inshirah Sgayer","doi":"10.1016/j.placenta.2024.11.015","DOIUrl":"10.1016/j.placenta.2024.11.015","url":null,"abstract":"<div><h3>Introduction</h3><div>To compare histopathological findings of placentas of dichorionic diamniotic twin pregnancies of in-vitro fertilization (IVF), conceived after fresh embryo transfer (ET) and frozen-thawed ET.</div></div><div><h3>Methods</h3><div>This retrospective study compared dichorionic diamniotic twin IVF pregnancies that resulted in livebirths during 2010–2022. The placental findings were classified according to definitions curated by the 2016 Amsterdam Placental Workshop Group Consensus Statement. A multivariate logistic analysis was constructed to estimate the odds ratios (OR) of placental histopathology abnormal findings, adjusted for maternal age, body mass index and nulliparity.</div></div><div><h3>Results</h3><div>The mean gestational age at birth was lower following fresh ET pregnancies (n = 236) than frozen-thawed ET pregnancies (n = 122) (34.89 vs 35.77 weeks, p = 0.003). For the fresh ET compared to the frozen-thawed ET group, rates were higher of preterm birth (69.5 % vs. 55.7 %, p = 0.011), low birthweight (71.6 % vs 57.4 %, p < 0.001) and very low birthweight (14.2 % vs 9.0 %, p value one sided = 0.029). For the fresh ET compared with the frozen-thawed ET group, the rates were higher of maternal vascular lesions (20.3 % vs. 11.5 %, p = 0.003), placental hemorrhage (12.7 % vs. 7 %, p = 0.021), and villous lesions related to maternal vascular lesions (7.2 % vs. 3.7 %, p value one sided = 0.04). A multivariate logistic analysis showed a higher risk of maternal or neonatal vascular lesions for twin pregnancies after fresh ET than frozen-thawed ET (adjusted OR = 1.91, 95 % CI 1.26–2.92, p = 0.011).</div></div><div><h3>Conclusions</h3><div>Following fresh ET compared to frozen-thawed ET, obstetrical and neonatal outcomes were worse, and the risk of maternal vascular lesions was greater.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"159 ","pages":"Pages 47-51"},"PeriodicalIF":3.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142757606","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}