PlacentaPub Date : 2024-12-08DOI: 10.1016/j.placenta.2024.12.004
Marina White, David Grynspan, Jayden Arif-Pardy, Tim Van Mieghem, Kristin L Connor
{"title":"Altered placental phenotype and increased risk of placental pathology in fetal spina bifida: A matched case-control study.","authors":"Marina White, David Grynspan, Jayden Arif-Pardy, Tim Van Mieghem, Kristin L Connor","doi":"10.1016/j.placenta.2024.12.004","DOIUrl":"https://doi.org/10.1016/j.placenta.2024.12.004","url":null,"abstract":"<p><strong>Introduction: </strong>Spina bifida (SB) remains one of the most common congenital anomalies and associates with significant comorbidities in the fetus, which may, in part, be driven by placental maldevelopment. We hypothesised that placental pathologies would be more prevalent in fetuses with SB compared to fetuses without congenital anomalies.</p><p><strong>Methods: </strong>Placental pathology and transcriptome were evaluated for fetuses with isolated open SB born preterm (cases; n = 12) and control fetuses without congenital anomalies (n = 22) born at full term (FT) or preterm (PT). We evaluated associations between study group and placental histopathology, and between placental histopathology and gene expression.</p><p><strong>Results: </strong>Placental weight was lower in cases than PT controls (median [IQR]: 263 g [175, 370] vs. 455 g [378, 560], p = 0.001). Placental villi structural phenotype was different in cases, where proportion of immature intermediate villi was higher in cases than PT controls (32.5 % [6.3, 56.3] vs. 10 % [5, 13.8], p = 0.01), but cases and FT controls had similar proportions of mature intermediate (10 % [5, 10] vs. 10 % [8.75, 11.25]) and terminal villi (22.5 % [11.3, 43.8] vs. 30 % [20, 36.3]), and similar odds of having many syncytial knots (adjusted odds ratio [aOR] = 6 [0.2, 369]). Case placentae also had higher odds of having many Hofbauer cells (aOR = 16.2 [1.4, 580], p = 0.02) and a thick syncytial membrane (aOR = 146 [3, 3.46e5], p = 0.007). Gene expression in immune/inflammatory processes, spinal cord injury, and Hedgehog and Wnt signaling pathways were associated with placental maturity in cases.</p><p><strong>Discussion: </strong>Improved knowledge on placental phenotypes in SB increases our understanding of mechanisms that may drive comorbidities, and may ultimately inform efforts to reduce offspring morbidity and mortality.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"159 ","pages":"107-118"},"PeriodicalIF":3.0,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829859","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}
PlacentaPub Date : 2024-12-04DOI: 10.1016/j.placenta.2024.12.002
Leena Kadam, Marija Veličković, Kelly Stratton, Carrie D Nicora, Jennifer E Kyle, Eric Wang, Matthew E Monroe, Lisa M Bramer, Leslie Myatt, Kristin E Burnum-Johnson
{"title":"Sexual dimorphism in lipidomic changes in maternal blood and placenta associated with obesity and gestational diabetes: A discovery study.","authors":"Leena Kadam, Marija Veličković, Kelly Stratton, Carrie D Nicora, Jennifer E Kyle, Eric Wang, Matthew E Monroe, Lisa M Bramer, Leslie Myatt, Kristin E Burnum-Johnson","doi":"10.1016/j.placenta.2024.12.002","DOIUrl":"10.1016/j.placenta.2024.12.002","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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>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.</p><p><strong>Results: </strong>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.</p><p><strong>Discussion: </strong>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.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"159 ","pages":"76-83"},"PeriodicalIF":3.0,"publicationDate":"2024-12-04","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}
PlacentaPub Date : 2024-12-04DOI: 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":"https://doi.org/10.1016/j.placenta.2024.12.001","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Discussion: </strong>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.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"159 ","pages":"70-75"},"PeriodicalIF":3.0,"publicationDate":"2024-12-04","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}
{"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}
PlacentaPub Date : 2024-11-26DOI: 10.1016/j.placenta.2024.11.007
Samantha Lapehn, Sidharth Nair, Evan J Firsick, James MacDonald, Ciara Thoreson, James A Litch, Nicole R Bush, Leena Kadam, Sylvie Girard, Leslie Myatt, Bhagwat Prasad, Sheela Sathyanarayana, Alison G Paquette
{"title":"A transcriptomic comparison of in vitro models of the human placenta.","authors":"Samantha Lapehn, Sidharth Nair, Evan J Firsick, James MacDonald, Ciara Thoreson, James A Litch, Nicole R Bush, Leena Kadam, Sylvie Girard, Leslie Myatt, Bhagwat Prasad, Sheela Sathyanarayana, Alison G Paquette","doi":"10.1016/j.placenta.2024.11.007","DOIUrl":"10.1016/j.placenta.2024.11.007","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>All in vitro placental models had a substantial number of differentially expressed genes (DEGs, FDR<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.</p><p><strong>Discussion: </strong>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)\".</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"159 ","pages":"52-61"},"PeriodicalIF":3.0,"publicationDate":"2024-11-26","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PlacentaPub Date : 2024-11-26DOI: 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":"https://doi.org/10.1016/j.placenta.2024.11.014","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Discussion: </strong>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.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"159 ","pages":"62-69"},"PeriodicalIF":3.0,"publicationDate":"2024-11-26","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PlacentaPub Date : 2024-11-25DOI: 10.1016/j.placenta.2024.11.013
Minako Goto, Kohei Seo, Ayumi Okuyama, Kiyotake Ichizuka
{"title":"\"Umbilical artery Doppler in severe small for gestational age: Prognostic insights for short and long-term neurodevelopment\"","authors":"Minako Goto, Kohei Seo, Ayumi Okuyama, Kiyotake Ichizuka","doi":"10.1016/j.placenta.2024.11.013","DOIUrl":"10.1016/j.placenta.2024.11.013","url":null,"abstract":"<div><h3>Introduction</h3><div>We evaluated the impact of absent end-diastolic flow in the umbilical artery (UA-AEDF) in severe small for gestational age (SGA) cases.</div></div><div><h3>Methods</h3><div>This retrospective cohort study focused on fetuses with severe SGA (defined as birth weight ≤2.5 SD). Clinical measurements and neonatal outcomes were compared between the UA-AEDF and non-UA-AEDF groups.</div></div><div><h3>Results</h3><div>Fifty-four patients were categorized into UA-AEDF (15 patients) and non-UA-AEDF (39 patients) groups. Regarding neonatal short-term prognosis, the UA-AEDF group showed higher rates of respiratory distress syndrome (RDS), late circulatory dysfunction, late metabolic acidosis, and retinopathy of prematurity (ROP) requiring laser treatment than the non-UA-AEDF group. However, within 32 weeks of gestation, the complication rates between the two groups were not significantly different. In the 32 weeks before delivery, the overall developmental quotient (DQ) scores of children in the UA-AEDF group were lower than those in the non-UAAEDF group. Specifically, within the UA-AEDF group, the mean DQ scores at 1.5 years of corrected age was significantly lower prior to 32 weeks of gestation than in the other groups.</div></div><div><h3>Discussion</h3><div>This study demonstrated that UA-AEDF in severely SGA infants before 32 weeks of gestation may be associated with poor long-term prognosis, comparable to preterm infants. Conversely, in non-UA-AEDF cases, the frequency of poor long-term prognosis, involving DQ, remained consistent before and after 32 weeks of gestation. This study highlights the potential significance of UA-AEDF in predicting neurodevelopmental outcomes in severe SGA infants; thus, incorporating UA Doppler findings into clinical protocols for severe SGA cases is helpful.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"159 ","pages":"Pages 32-38"},"PeriodicalIF":3.0,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745190","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 : 2024-11-23DOI: 10.1016/j.placenta.2024.11.009
Ping Yang , Xinyang Liu , Jinli Lyu , Qiaoli Feng , Yuzhen Ding , Shilin Zhong , Ping Liu , Yiheng Liang , Chunfeng Liu , Liting Huang , Pingyue Zhao , Qing Li , Kaidong Ma , Shangrong Fan , Xiaowei Zhang
{"title":"Down-regulation of TAGLN2 associated with the development of preeclampsia by effecting the Rap1 signaling pathway","authors":"Ping Yang , Xinyang Liu , Jinli Lyu , Qiaoli Feng , Yuzhen Ding , Shilin Zhong , Ping Liu , Yiheng Liang , Chunfeng Liu , Liting Huang , Pingyue Zhao , Qing Li , Kaidong Ma , Shangrong Fan , Xiaowei Zhang","doi":"10.1016/j.placenta.2024.11.009","DOIUrl":"10.1016/j.placenta.2024.11.009","url":null,"abstract":"<div><h3>Introduction</h3><div>Preeclampsia (PE) poses significant global challenges to pregnancy health, being a leading cause of maternal and perinatal morbidity and mortality. Unfortunately, effective treatment options remain limited, necessitating the urgent development of novel therapeutic strategies. This study is to investigate down-regulation of Transgelin-2 (TAGLN2) contributes to the development of PE through suppression of the Rap1 signaling pathway.</div></div><div><h3>Methods</h3><div>Placentas from PE patients were collected for a transcriptome analysis. Down-regulation experiments of TAGLN2 were performed in mouse and HTR-8/SVneo cells to generate PE models. The mechanism by which down-regulation of TAGLN2 induces PE was explored based on these PE model through transcriptome and proteome analysis and molecular tests.</div></div><div><h3>Results</h3><div>Our findings revealed that the expression levels of Rap1A was significantly reduced in the placenta of PE patients. The expression level of Rap1A in the placental tissue of sh_Tagln2 PE model mice is down-regulated. In addition, TAGLN2 down-regulation impede the proliferation and migration of HTR8/SVneo cells and lead to the decreased expression of Rap1A. Meanwhile, Rap1A down-regulation impede both the proliferation and migration of HTR8/SVneo cells. Both transcriptomic and proteomic levels of sh-TG2 HTR8/Svneo cells demonstrated Rap1 signaling pathway and related key genes was inhibited after TAGLN2 down-regulation.</div></div><div><h3>Conclusion</h3><div>Our results confirm that down-regulation of TAGLN2 in HTR-8/SVneo cells leads to the decreased Rap1A expression and suppresses trophoblast cell proliferation and migration by inhibiting Rap1 signaling pathway. Meanwhile, Rap1A down-regulation impede both the proliferation and migration of HTR8/SVneo cells. These findings concluded that down-regulation of TAGLN2 may be implicated in the development of preeclampsia through its effect on the Rap1 signaling pathway.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"159 ","pages":"Pages 20-31"},"PeriodicalIF":3.0,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740149","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 : 2024-11-22DOI: 10.1016/j.placenta.2024.11.012
Te-Yao Hsu , Chih-Chang Tsai , Hsin-Hsin Cheng , Kuo-Chung Lan , Hsuan-Ning Hung , Wan-Ting Huang , Yun-Ju Lai , Kun-Long Huang , Huey-Ling You , Ping-Chung Tsai , Chia-Ing Jan , Sung-Chou Li
{"title":"Lower level of miR-34a leads to placenta accreta spectrum by promoting the proliferation, migration of trophoblast villous epithelial cells and enhanced the angiogenesis of vascular endothelial cells","authors":"Te-Yao Hsu , Chih-Chang Tsai , Hsin-Hsin Cheng , Kuo-Chung Lan , Hsuan-Ning Hung , Wan-Ting Huang , Yun-Ju Lai , Kun-Long Huang , Huey-Ling You , Ping-Chung Tsai , Chia-Ing Jan , Sung-Chou Li","doi":"10.1016/j.placenta.2024.11.012","DOIUrl":"10.1016/j.placenta.2024.11.012","url":null,"abstract":"<div><h3>Introduction</h3><div>The overall prevalence of placenta accreta spectrum (PAS) is approximately 0.17 %, but it accounts for 7 % of maternal mortality and is associated with intraoperative and postoperative morbidity. The pathogenesis mechanisms of PAS include an imbalance between decidualization and trophoblast invasion. The aim of this study is to identify the pathogenesis roles of miR-34a in PAS.</div></div><div><h3>Methods</h3><div>For this purpose, we collected 15 placenta tissues from pregnant subjects with PAS complications and another 15 placenta tissues from normal pregnancy (NP) cases. Then, we conducted <em>in situ</em> hybridization assay to compare miR-34a expression level, followed by <em>in vitro</em> simulations of NP and PAS with miR-34a and scrambled control (SC) mimic transfection in cells, respectively. Next, we conducted <em>in vitro</em> cellular assays to investigate the pathogenesis mechanisms of miR-34a in PAS.</div></div><div><h3>Results</h3><div>We first confirmed significantly lower level of miR-34a in the trophoblast villous (TV) from PAS patients. By <em>in vitro</em> assays, lower miR-34a led to significantly higher cell proliferation and enhanced cell migration in TV epithelial cells. In addition, lower miR-34a resulted in elevated angiogenesis ability in vascular endothelial cells. Finally, to identify the pathway involved by miR-34a in PAS, we used microarray (raw data available via NCBI GEO database with accession number <span><span>GSE279257</span><svg><path></path></svg></span>) and flow cytometry to confirm that lower miR-34a significantly repressed the apoptosis activity in TV epithelial cells.</div></div><div><h3>Discussion</h3><div>In this study, we not only confirmed miR-34a as a biomarker of PAS but also clarified the <em>in vitro</em> pathogenesis mechanism of miR-34a in PAS.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"159 ","pages":"Pages 1-8"},"PeriodicalIF":3.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740245","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}