PlacentaPub Date : 2025-02-19DOI: 10.1016/j.placenta.2025.02.010
Salma El Emrani , Jacqueline U.M. Termote , Esther J.S. Jansen , Jelle J. Goeman , Enrico Lopriore , Nicoline E. Schalij-Delfos , Lotte E. van der Meeren
{"title":"Difference in adverse neonatal outcomes between preterm singletons and twins possibly explained by placental abnormalities","authors":"Salma El Emrani , Jacqueline U.M. Termote , Esther J.S. Jansen , Jelle J. Goeman , Enrico Lopriore , Nicoline E. Schalij-Delfos , Lotte E. van der Meeren","doi":"10.1016/j.placenta.2025.02.010","DOIUrl":"10.1016/j.placenta.2025.02.010","url":null,"abstract":"<div><h3>Introduction</h3><div>The purpose of this study was to compare microscopic placental characteristics between preterm twins and singletons, and between preterm monochorionic and dichorionic twins, in order to explore the effect of placental pathology on adverse neonatal outcomes.</div></div><div><h3>Methods</h3><div>This study included 566 neonates born ≤32 weeks and/or ≤1500 g, of whom 429 were singletons and 137 were twins (38 monochorionic and 99 dichorionic). Clinical data was retrospectively collected, and placentas were prospectively examined for maternal vascular malperfusion, fetal vascular malperfusion and placental inflammation (acute and chronic).</div></div><div><h3>Results</h3><div>Singletons had increased rates of maternal vascular malperfusion, fetal hypoxia, funisitis (in umbilical cord and chorial plate), chronic deciduitis, and villitis of unknown etiology compared to twins. Delayed villous maturation and ischemia were more frequently present in monochorionic placentas than in dichorionic. Singletons had a significant lower birthweight and were more often small for gestational age than twins. Multivariate linear regression analysis adjusting for singleton pregnancy, gestational hypertension and placental abnormalities showed that gestational hypertension (β = −114.8), infarct (β = −130.1), decidual necrosis (β = −115.4), fetal hypoxia (β = −59.3) and chronic deciduitis (β = −118.8) were independently associated with lower birthweight. Multivariate regression analysis revealed five independent risk factors of small for gestational age: gestational hypertension (OR 4.4), infarct (OR 3.7), decidual necrosis (OR 2.7), fetal hypoxia (OR 1.9) and villitis (OR 5.2).</div></div><div><h3>Discussion</h3><div>Singleton pregnancies vary in histological placental abnormality rates from twin pregnancies. This study demonstrated that differences in birthweight and small for gestational age rates between preterm twins and singletons can be attributed to gestational hypertension and histological placental abnormalities.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"162 ","pages":"Pages 45-50"},"PeriodicalIF":3.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487217","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 : 2025-02-17DOI: 10.1016/j.placenta.2025.02.012
Aneya Sousa , Ojong Tabi Ojong Besong , Elisha M. Wachman , Elizabeth S. Taglauer , Jennifer E. Beane , Yohana Kefella , Ji Sun Koo , Kelley Saia , Hendree E. Jones , Huiping Zhang
{"title":"Placental transcriptome analysis in opioid-exposed versus non-opioid exposed pregnancies","authors":"Aneya Sousa , Ojong Tabi Ojong Besong , Elisha M. Wachman , Elizabeth S. Taglauer , Jennifer E. Beane , Yohana Kefella , Ji Sun Koo , Kelley Saia , Hendree E. Jones , Huiping Zhang","doi":"10.1016/j.placenta.2025.02.012","DOIUrl":"10.1016/j.placenta.2025.02.012","url":null,"abstract":"<div><h3>Introduction</h3><div>Opioid exposure during pregnancy may significantly alter gene expression in the placenta, potentially disrupting its function and influencing fetal brain development. These alterations may contribute to adverse outcomes such as neonatal opioid withdrawal syndrome (NOWS). In this study, we aim to systematically investigate the changes in placental gene expression associated with maternal opioid exposure to better understand the underlying molecular mechanisms and their implications for fetal health.</div></div><div><h3>Methods</h3><div>Fresh placental tissue samples were collected from 18 opioid-exposed pregnancies and 26 non-opioid-exposed control pregnancies. Transcriptomic changes related to opioid exposure were assessed using RNA sequencing (RNA-seq).</div></div><div><h3>Results</h3><div>Among the 16,172 genes detected, 55 showed differential expression (<em>P</em><sub>adjusted</sub> < 0.25 or <em>P</em><sub>unadjusted</sub> < 0.001) in opioid-exposed placentas. Gene Set Enrichment Analysis (GSEA) revealed that the differentially expressed genes were primarily associated with immune responses, neuronal development and function, as well as cell replication and division. Computational deconvolution using the PlacentaCellEnrich program identified significant enrichment of upregulated genes in decidual NK cells. Furthermore, integrative analysis of DNA methylation and gene expression showed an enrichment of differentially methylated genes among downregulated genes in opioid-exposed placentas.</div></div><div><h3>Discussion</h3><div>Our findings suggest that opioid exposure during pregnancy may disrupt critical placental pathways, particularly those involved in immune responses. Future studies focusing on transcriptomic changes in specific placental cell types will be essential for fully understanding the structural and functional alterations in the placenta due to opioid exposure during pregnancy.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"162 ","pages":"Pages 27-34"},"PeriodicalIF":3.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445615","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 : 2025-02-13DOI: 10.1016/j.placenta.2025.02.008
Joseph Byrne , Niccole Ranaei-Zamani , J. Ciaran Hutchinson , Sara Hillman
{"title":"A retrospective analysis of placental histopathological findings in gestational diabetes mellitus (GDM)","authors":"Joseph Byrne , Niccole Ranaei-Zamani , J. Ciaran Hutchinson , Sara Hillman","doi":"10.1016/j.placenta.2025.02.008","DOIUrl":"10.1016/j.placenta.2025.02.008","url":null,"abstract":"<div><h3>Introduction</h3><div>The placenta plays a pivotal role in supporting fetal growth and disruptions in its development and function can impact fetal outcomes. While placental pathology has been extensively studied in clinical conditions such as pre-eclampsia and fetal growth restriction (FGR), the association between placental abnormalities and gestational diabetes mellitus (GDM) is still unclear. This study aims to explore the placental pathology associated with GDM, shedding light on potential links to adverse perinatal outcomes.</div></div><div><h3>Methods</h3><div>A retrospective cohort study was conducted using electronic patient data from the Fetal Medicine and Neonatal Units at University College London Hospital. Placental samples were obtained and analysed at Great Ormond Street Hospital. Maternal demographics, obstetric history and placental histopathology were reviewed. Statistical analyses were performed to identify associations and risk factors.</div></div><div><h3>Results</h3><div>Of the 2580 pregnancies analysed, 341 were GDM pregnancies, 549 had FGR and 66 had both GDM and FGR. GDM pregnancies required increased rates of obstetric intervention and neonatal care admission. Placental pathology in GDM revealed a higher prevalence of maternal vascular malperfusion (MVM) lesions, whilst GDM-related FGR showed further associations with MVM lesions and adverse perinatal outcomes.</div></div><div><h3>Discussion</h3><div>Our study highlights MVM lesions as a prominent feature in the placentas of GDM pregnancies, especially when associated with FGR. These lesions are linked to adverse perinatal outcomes, emphasizing the need for enhanced antenatal care in these cases. The study contributes insights into the complex relationship between GDM, placental pathology and adverse fetal outcomes, laying the foundation for future investigations into early interventional strategies.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"162 ","pages":"Pages 20-26"},"PeriodicalIF":3.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419969","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 : 2025-02-11DOI: 10.1016/j.placenta.2025.02.006
Stacy Zamudio, Nicholas P Illsley
{"title":"Research design and tissue collection considerations for investigation of placenta accreta spectrum.","authors":"Stacy Zamudio, Nicholas P Illsley","doi":"10.1016/j.placenta.2025.02.006","DOIUrl":"https://doi.org/10.1016/j.placenta.2025.02.006","url":null,"abstract":"<p><p>Placenta accreta spectrum (PAS) is a group of pregnancy pathologies characterized by loss/absence of decidua and trophoblast over-invasion penetrating into the myometrium beyond the normal depth. It is associated with expansion of deeper branches of the uterine arteries and placental adherence to the uterus. Undetected PAS leads frequently to massive and potentially fatal hemorrhage at delivery. For the more severe forms of PAS (increta, percreta), the most frequent solution is caesarean delivery-hysterectomy. The etiology of PAS is, however, unclear at best. While there is increasing research interest, the clinical intricacies of this pathology pose significant challenges for the researcher. In this communication we present the elements which we believe should be considered when undertaking (or interpreting) research into PAS, particularly when biological samples and molecular techniques are involved.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433637","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 : 2025-02-11DOI: 10.1016/j.placenta.2025.02.007
Ragnheidur I. Bjarnadottir , Thora Steffensen , Karin Pettersson , Nikos Papadogiannakis , Alexander K. Smarason , Johanna Gunnarsdottir
{"title":"Stillbirth at term in Iceland: Causes of death and patterns of placental injury","authors":"Ragnheidur I. Bjarnadottir , Thora Steffensen , Karin Pettersson , Nikos Papadogiannakis , Alexander K. Smarason , Johanna Gunnarsdottir","doi":"10.1016/j.placenta.2025.02.007","DOIUrl":"10.1016/j.placenta.2025.02.007","url":null,"abstract":"<div><h3>Background</h3><div>Iceland is a high-income country with <400.000 inhabitants and low stillbirth rate (SBR). Increased antenatal risk assessment and interventions in high-risk pregnancies doubled the induction rate after 2008.</div></div><div><h3>Objective</h3><div>Estimate the SBR at term, comparing an earlier (1996–2008) and latter (2009–2021) 13-year period, and describe causes of death and patterns of placental injury of infants stillborn at term.</div></div><div><h3>Study design</h3><div>Stillbirth at term was defined as antepartum or intrapartum death of an infant that was diagnosed after ≥37 weeks of gestation. All cases (n = 125) had placental examination. Histopathological slides were reviewed, and pattern of placental injury classified according to the Amsterdam consensus. Medical records were found for all mothers who had stillbirth at term and cause of death assigned according to the Stockholm classification of stillbirth.</div></div><div><h3>Results</h3><div>No decrease in the SBR at term was found between periods. Majority of deaths (72 %) were caused by cord complications and/or placental insufficiency and deaths attributed to placental insufficiency increased in the latter period. Placentas weighing under the 10th percentile were more common in the latter period, 43.5 % vs. 30.2 % (p < 0.05) as was chronic villitis of unknown etiology (VUE), 40.3 % vs. 12.7 % (p < 0.01).</div></div><div><h3>Conclusion</h3><div>Stillbirth at term has not decreased in Iceland, despite increased antenatal surveillance and induction rate, with more deaths attributed to placental insufficiency and VUE increasingly found in the later period. Further research is needed on the correlation of patterns of placental injury with clinical phenotypes of mothers and infants.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"162 ","pages":"Pages 14-19"},"PeriodicalIF":3.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419968","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":"Pulmonary trophoblastic deportation in the hystricomorph rodent Lagostomus maximus","authors":"Francisco Acuña , Gimena Gomez Castro , Daniel González Gómez , Agostina Terraza , Mirta Alicia Flamini , Claudio Gustavo Barbeito","doi":"10.1016/j.placenta.2025.02.004","DOIUrl":"10.1016/j.placenta.2025.02.004","url":null,"abstract":"<div><h3>Introduction</h3><div>Trophoblast has been reported in the lungs of gestating eutherian mammals with hemochorial placenta, including humans, cotton rats, and American hares. This study describes the discovery of trophoblastic-like cells in the lungs of <em>Lagostomus maximus</em>.</div></div><div><h3>Methods</h3><div>Lung and placenta samples from non-pregnant and pregnant plains viscachas were analyzed using histology and immunohistochemistry.</div></div><div><h3>Results</h3><div>Macroscopically, the lungs of females in both groups showed no alterations, but microscopic examination of the lungs from pregnant females revealed lesions and trophoblast-like cells. Markers such as pancytokeratin, MMP-2, MMP-9, and progesterone receptors were found in both pulmonary trophoblastic cells and the various types of trophoblasts in the placenta and subplacenta. Notably, cytokeratin-7 showed similarity with the placenta but not with the subplacenta. Cells identified in the lungs that were positive for markers similar to trophoblast giant cells in the maternal blood chambers suggest that the trophoblast that reaches the lungs may originate from giant cells that enter maternal blood circulation rather than those that invade the uterine artery. Immunohistochemical analysis indicated that, unlike placental trophoblast, the lung cells exhibited no proliferative activity.</div></div><div><h3>Discussion</h3><div>The lack of this process in mice and the difficulty of developing <em>in vivo</em> experimental models have prompted the exploration of <em>in vitro</em> models. <em>L. maximus</em> may serve as an alternative model to study this process, necessitating further research to determine the timing of this phenomenon during gestation and whether pulmonary alterations persist after parturition.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"162 ","pages":"Pages 1-8"},"PeriodicalIF":3.0,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143395644","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":"Coagulation and fibrinolytic system of umbilical venous blood in hyper-coiled umbilical cord: A single center cohort study","authors":"Shota Saji , Masatomo Doi , Junki Koike , Nao Suzuki , Junichi Hasegawa","doi":"10.1016/j.placenta.2025.02.003","DOIUrl":"10.1016/j.placenta.2025.02.003","url":null,"abstract":"<div><h3>Introduction</h3><div>We aimed to clarify whether the coagulation-fibrinolytic system is activated in a hyper-coiled umbilical cord (HCC).</div></div><div><h3>Methods</h3><div>This prospective cohort study was conducted at a single perinatal center in Japan, including singleton pregnant women who delivered after 37 weeks of gestation between January and July 2024. Umbilical venous blood was collected immediately after birth and before placental delivery. The coagulation and fibrinolytic systems were measured, and variables were compared between patients with and without HCC.</div></div><div><h3>Results</h3><div>As a variable of cell blood count and hemostatic function, platelet concentration was significantly lower in the HCC group [median (range): 25.5 (17.3–32.1) vs 30.4 (18.5–39.55) x100000/μl, p = 0.020]. For coagulation variables, fibrinogen concentration [105 (63–116) vs 137.5 (56–229) mg/dl, p < 0.001] and antithrombin III [35 (27–51) vs 47.5 (31–62) %, p = 0.022] were significantly lower in the HCC group. Regarding fibrinolytic variables, plasmin inhibitor complex concentration was significantly higher in HCC group [1.3 (1.0–6.9) vs 0.7 (0.3–5.2) μg/ml, p = 0.036]; however, plasminogen concentration was significantly lower in HCC group [40 (32–46) vs 50 (25–64), p < 0.001].</div></div><div><h3>Discussion</h3><div>This is the first report where the coagulation-fibrinolytic system in the umbilical venous blood in cases with HCC was demonstrated. Findings reveal an activated coagulation-fibrinolytic system even in cases without severe fetal growth restriction due to HCC after 37 weeks of gestation.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"162 ","pages":"Pages 9-13"},"PeriodicalIF":3.0,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143395772","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 : 2025-02-06DOI: 10.1016/j.placenta.2025.02.002
María S Martinez, Yair A Chocobar, Yamila Fariz, Daniela A Paira, Virginia E Rivero, Rubén D Motrich
{"title":"Effects of semen inflammation on embryo implantation, placentation, pregnancy outcomes and offspring health.","authors":"María S Martinez, Yair A Chocobar, Yamila Fariz, Daniela A Paira, Virginia E Rivero, Rubén D Motrich","doi":"10.1016/j.placenta.2025.02.002","DOIUrl":"https://doi.org/10.1016/j.placenta.2025.02.002","url":null,"abstract":"<p><p>This review explores the critical role of semen inflammation in sperm quality, embryo implantation, placentation, and its broader implications on reproductive health. Chronic inflammation of the male genital tract has been increasingly recognized as a significant factor contributing to infertility. This inflammation not only impairs semen quality but also disrupts the intricate immune cross-talk between the male and female genital tracts, which is essential for successful implantation, placentation and pregnancy. The review synthesizes existing research on the mechanisms by which inflammatory mediators in semen influence the female immune environment, leading to altered uterine receptivity, placental formation, and embryo implantation. Furthermore, the impact of these disruptions on the health and development of the offspring is discussed, highlighting the transgenerational effects of male genital tract inflammation. Through an examination of both animal models and human studies, this review underscores the need for a deeper understanding of the immune interactions in reproductive biology and the potential for novel therapeutic interventions aimed at mitigating the adverse outcomes associated with semen inflammation.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143409918","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 : 2025-02-06DOI: 10.1016/j.placenta.2025.02.001
Yollyseth Medina, Nazarena Fernandez, Matías N Sierra, Mauricio Castro Parodi, Alicia E Damiano
{"title":"Nitrative stress-induced dysregulation of placental AQUAPORIN-9: A potential key player in preeclampsia pathogenesis.","authors":"Yollyseth Medina, Nazarena Fernandez, Matías N Sierra, Mauricio Castro Parodi, Alicia E Damiano","doi":"10.1016/j.placenta.2025.02.001","DOIUrl":"https://doi.org/10.1016/j.placenta.2025.02.001","url":null,"abstract":"<p><p>Preeclampsia is associated with increased oxidative and nitrative stress, resulting in elevated protein nitration and potential functional impairment. Previously, we found an increased expression of AQP9 protein with a loss of function in preeclamptic placentas. However, the link between nitrative stress and AQP9 has not yet been explored. Here, we aimed to evaluate the effect of nitrative stress on placental AQP9 and its role in the pathogenesis of preeclampsia. In silico analysis was conducted on the amino acid sequences of AQP9 to identify potential nitration sites. Levels of 3NyT-AQP9 were assessed by immunoprecipitation in normal and preeclamptic placentas. AQP9 expression and function were evaluated by culturing normal placental explants with 0, 25, 50, 100, and 200 μM ONOO- to induce nitrative stress. Viability and integrity of the explants and stress markers were determined. Water uptake and utilization of lactate mediated by AQP9 were studied along with the molecular expression of AQP9 and 3-NyT-AQP9. The in silico analysis showed that AQP9 is more susceptible to nitration than other AQPs. The abundance of nitrated AQP9 significantly increased in preeclamptic placentas compared to normal ones (n = 4; p < 0.05). Peroxynitrite treatment also increased AQP9 protein expression without altering its gene expression and impaired the transport of water and lactate mediated by this protein. Our findings provide evidence that nitrative stress induces the nitration of AQP9 protein, leading to the accumulation of a non-functional protein in the syncytiotrophoblasts. Therefore, this altered protein may play a pivotal role in the pathogenesis of preeclampsia by disrupting cellular homeostasis.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425904","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 : 2025-02-05DOI: 10.1016/j.placenta.2025.02.005
Anna Li , Man Zhao , Ziming Lin , Zexin Yang , Pihai Gong , Chunying Wang , Zhenya Fang , Meihua Zhang
{"title":"Reduced SMEK1 regulates trophoblast migration and invasion in fetal growth restriction","authors":"Anna Li , Man Zhao , Ziming Lin , Zexin Yang , Pihai Gong , Chunying Wang , Zhenya Fang , Meihua Zhang","doi":"10.1016/j.placenta.2025.02.005","DOIUrl":"10.1016/j.placenta.2025.02.005","url":null,"abstract":"<div><h3>Introduction</h3><div>Fetal growth restriction (FGR) is a significant pregnancy condition characterized by the fetus failing to attain its full genetic growth potential. FGR is primarily ascribed to defective placentation, owing to impaired trophoblast cellular function. The objective of this research is to elucidate the pathogenic functions of suppressor of Mek1 (SMEK1) in FGR.</div></div><div><h3>Methods</h3><div>Western blot and Immunofluorescence were used to detect the expression and localization of SMEK1 in placenta. We overexpressed and knocked down SMEK1 using plasmid or siRNA special targeted it. EdU Assay, flow cytometry, Western blot, Wound healing migration and Transwell insert assay were used to detect the influence of SMEK1 on cellular function. The mechanism of SMEK1 in regulating the migration of JEG3 cells was predicted by employing transcriptomics and bioinformatics analysis, and was validated by Western blot.</div></div><div><h3>Results</h3><div>The expression of SMEK1 was downregulated in FGR placentas. The aberrant expression of SMEK1 in JEG3 cells is associated with cell migration and invasion, but not with proliferation, or apoptosis. Transcriptomic analysis and Western blots indicate that knockdown of SMEK1 inhibited the PI3K/Akt/mTOR pathway. A significant inhibition was observed in the epithelial-mesenchymal transition (EMT) process of JEG3 cells within the SMEK1 knockdown group. The activation of the PI3K/Akt/mTOR pathway partially restored the impaired migration and invasive ability due to SMEK1 knockdown in JEG3 cells.</div></div><div><h3>Discussion</h3><div>the reduction of SMEK1 may contribute to the development of FGR by hindering the EMT process of trophoblast cells through modulation of the PI3K/Akt/mTOR signaling pathway.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"161 ","pages":"Pages 65-75"},"PeriodicalIF":3.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143377041","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}