Placenta最新文献

{"title":"Midpregnancy maternal circulating angiogenic biomarkers: Associations with placental dysfunction-related pregnancy complications and fetal sex","authors":"Birgitte Kordt Sundet ,&nbsp;Karin C. Lødrup Carlsen ,&nbsp;Guttorm Haugen ,&nbsp;Gunilla Hedlin ,&nbsp;Katarina Hilde ,&nbsp;Christine M. Jonassen ,&nbsp;Björn Nordlund ,&nbsp;Eva Maria Rehbinder ,&nbsp;Corina Silvia Rueegg ,&nbsp;Katrine Sjøborg ,&nbsp;Håvard O. Skjerven ,&nbsp;Cilla Söderhäll ,&nbsp;Riyas Vettukattil ,&nbsp;Magdalena R. Værnesbranden ,&nbsp;Johanna Wiik ,&nbsp;Anne Cathrine Staff ,&nbsp;Meryam Sugulle","doi":"10.1016/j.placenta.2025.09.006","DOIUrl":"10.1016/j.placenta.2025.09.006","url":null,"abstract":"<div><h3>Introduction</h3><div>Placental function differs by fetal sex, and placental dysfunction is associated with adverse pregnancy outcomes. We aimed to investigate the role of midpregnancy maternal circulating placenta-associated angiogenic biomarkers and fetal sex in relation to placental dysfunction-related pregnancy complications.</div></div><div><h3>Methods</h3><div>The Preventing Atopic Dermatitis and Allergies in children birth cohort study provided maternal serum from 2511 pregnancies at gestational weeks 16–22. Placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were analyzed by immunoassays. Pregnancy complications (n = 385) included gestational hypertension, preeclampsia, preterm delivery, and/or newborn weight &lt;10th percentile; categorized as ‘uncomplicated’, ‘complicated’ and ‘severely complicated’ pregnancies by zero, one or two or more complications. The risk of ‘any number of pregnancy complications’ by biomarkers tertiles were assessed in multivariable logistic regression models with interaction analyses of fetal sex.</div></div><div><h3>Results</h3><div>Midpregnancy median PlGF was lower and sFlt-1 higher in pregnancies with a female versus a male fetus, with median (interquartile range) sFlt-1/PlGF-ratio being 7.2 (4.9–10.2) versus 6.4 (4.3–9.0) in ‘uncomplicated’, 7.3 (4.7–10.7) versus 6.4 (4.5–9.0) in ‘complicated’, and 11.2 (5.4–22.7) versus 5.9 (4.8–13.4) in ‘severely complicated’ pregnancies. The risks of ‘any number of pregnancy complications’ were highest in the lowest tertile of PlGF (adjusted odds ratio (aOR) 1.6, 95 % confidence interval (CI): 1.2–2.2) and sFlt-1 (aOR 1.4, 95 % CI: 1.0–1.9) without influence of fetal sex (all, p_interactions &gt;0.05).</div></div><div><h3>Conclusion</h3><div>Circulating midpregnancy placenta-associated angiogenic biomarkers differed by fetal sex and pregnancy complications. The higher risk of pregnancy complications with low midpregnancy PlGF and/or sFlt-1 levels was not influenced by fetal sex.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"171 ","pages":"Pages 52-61"},"PeriodicalIF":2.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086974","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":"Decreased placental growth factor levels precede the onset of gestational diabetes mellitus: Insights into placental dysfunction and endothelial pathophysiology","authors":"Keisuke Nakajima,&nbsp;Keiichi Kumasawa,&nbsp;Motoaki Kinugawa,&nbsp;Kazunari Nemoto,&nbsp;Mari Ichinose,&nbsp;Masatake Toshimitsu,&nbsp;Seisuke Sayama,&nbsp;Takahiro Seyama,&nbsp;Takayuki Iriyama,&nbsp;Yasushi Hirota,&nbsp;Yutaka Osuga","doi":"10.1016/j.placenta.2025.09.005","DOIUrl":"10.1016/j.placenta.2025.09.005","url":null,"abstract":"<div><h3>Aims</h3><div>Gestational diabetes mellitus (GDM) and preeclampsia (PE) are obstetric complications that share common pathophysiological features involving endothelial dysfunction. Previous studies suggest that GDM increases PE risk. While the roles of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are well-established in PE, their involvement in GDM remains unclear. To address this gap, we conducted a retrospective cohort study measuring serum levels of sFlt-1, PlGF, and their ratio before the diagnosis of GDM.</div></div><div><h3>Methods</h3><div>This study analyzed 830 pregnant women who underwent serum sFlt-1 and PlGF measurements between 18 and 22 weeks of gestation. GDM diagnosis was performed between approximately 22 - 28 weeks of gestation using a 75g OGTT, and patients were classified into GDM and control groups.</div></div><div><h3>Results</h3><div>PlGF levels were significantly lower in the GDM group than in the control group (median values: 231 vs. 260 pg/mL, p = 0.05). Conversely, no statistically significant differences were observed between the GDM and control groups in terms of serum sFlt-1 levels and the sFlt-1/PlGF ratio.</div></div><div><h3>Conclusions</h3><div>These findings suggest that PlGF may play a crucial role in GDM pathophysiology and that an imbalance between sFlt-1 and PlGF may be more pronounced in severe GDM.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"171 ","pages":"Pages 26-33"},"PeriodicalIF":2.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145047195","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":"Interplay of stromal cell-derived factor 2 and endoplasmic reticulum stress in the placenta: A review.","authors":"E Bevilacqua, C R R Rocha, H W Yung, G J Burton, A R Lorenzon","doi":"10.1016/j.placenta.2025.09.004","DOIUrl":"https://doi.org/10.1016/j.placenta.2025.09.004","url":null,"abstract":"<p><p>Disruption of endoplasmic reticulum (ER) homeostasis causes a condition known as \"ER stress\" that triggers a finely regulated response, the unfolded protein response (UPR), primarily associated with the restoration of normal ER function. Although the UPR is principally a pro-survival process, sustained and/or prolonged stress can induce cell death. ER stress has been observed in various gestational diseases and is associated with poor pregnancy outcomes. In this review, we examined the role of stromal cell-derived factor 2 (SDF2) in the UPR, particularly in placental cells. We highlight recent findings that enhance our understanding of the underlying molecular mechanisms and their influence on the balance between cell survival and death. Exploring how SDF2 affects cell survival and death during ER stress may be vital for developing therapeutic strategies aimed at preventing adverse disease outcomes during pregnancy.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075906","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":"Exposure to prenatal maternal stress is associated with epigenetic age acceleration and altered cell composition in the placenta: The QF2011 Queensland Flood Study","authors":"Ella O. Beraldo ,&nbsp;Amy M. Inkster ,&nbsp;Maria S. Peñaherrera ,&nbsp;E Magda Price ,&nbsp;Johanna Schuetz ,&nbsp;Élodie Portales-Casamar ,&nbsp;Sue Kildea ,&nbsp;Cathy Vaillancourt ,&nbsp;Suzanne King ,&nbsp;Wendy P. Robinson","doi":"10.1016/j.placenta.2025.09.003","DOIUrl":"10.1016/j.placenta.2025.09.003","url":null,"abstract":"<div><h3>Background</h3><div>Exposure to prenatal maternal stress (PNMS) <em>in utero</em> has been associated with several adverse perinatal outcomes, such as pre-term birth and perturbed cognitive development. As the interface between the fetal and maternal compartments during pregnancy, the placenta has been postulated to play a role in this process. We hypothesized that placental DNA methylation (DNAme) may be altered in association with natural disaster-mediated PNMS.</div></div><div><h3>Methods</h3><div>Pooled placental samples from the Queensland Flood Study, or QF2011, cohort (n = 105) were processed for assessment of DNAme using the Illumina Infinium MethylationEPIC BeadChip array.</div></div><div><h3>Results</h3><div>Overall, we did not find significant associations between placental DNAme and several stress measurements using linear modelling (FDR&lt;0.05 and Δβ&gt;0.03). While we found that XX placentas had slightly higher predicted cytotrophoblast to syncytiotrophoblast cell ratios than XY placentas (p = 0.01), this difference in cell ratio was not associated with PNMS exposure. However, we did observe associations between placental epigenetic age acceleration and all three types of PNMS investigated (objective hardship (QFOSS) (p = 0.03), subjective distress (COSMOSS) (p = 0.03), and maternal cognitive appraisal (CONSEQ) (p = 0.0005) scores).</div></div><div><h3>Conclusion</h3><div>The lack of large global impacts of PNMS on placental DNAme possibly indicates that the placenta can buffer moderate levels of maternal stress during pregnancy. It remains unclear what the impact of increased placental epigenetic age acceleration is on fetal development or perinatal outcomes and will require further investigation.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"171 ","pages":"Pages 16-25"},"PeriodicalIF":2.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145047194","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":"Insights into embryo-endometrium immune interactions.","authors":"Rosanna Ramhorst, Lourdes Materazzi, Ana Schafir, Lara Castagnola, Laura Fernández, Elizabeth Soczewski, Esteban Grasso, Gustavo Martinez, Diego Gnocchi, Antonio Cattaneo, Lautaro Tessari, Marcela Irigoyen, Claudia Perez Leirós, Soledad Gori","doi":"10.1016/j.placenta.2025.08.332","DOIUrl":"https://doi.org/10.1016/j.placenta.2025.08.332","url":null,"abstract":"<p><p>Embryo implantation requires a tight immune homeostatic control that activates regulatory circuits. One interlocutor is the embryo, which produces soluble ligands and expresses receptors for different autocrine and paracrine factors. The other interlocutor is the receptive endometrium, which produces mediators to regulate proliferation, differentiation, adhesion and invasiveness of the embryo, among other processes. Here, we are going to discuss experimental evidence regarding human embryo-endometrial dialogue and give a new insight of the relevance of the immune cells to coordinate embryo implantation. In this sense, decidualization of endometrial stromal cells is a multistep process that gives rise to mature decidual cells and senescent decidual cells. The first subpopulation secretes pro-implantation factors and begins migration by encapsulating the embryo. In turn, the second does not complete differentiation but rather suffers a process of premature senescence that is characterized by the production of pro-inflammatory factors (SASP, senescence-associated secretory phenotype), which contribute to embryo implantation. However, alterations in these processes or in their regulation through microRNAs lead to the perpetuation of an inflammatory response and alterations in endometrial receptivity. Considering that decidual cells acquire the ability to differentially respond to embryo quality, here we also explored how the soluble factors produced by embryos (classified according to their quality) impact on the inflammatory response and shape dendritic and other immune cell recruitment during the peri implantation period. To address these aspects, we present experimental evidence that links endoplasmic reticulum stress, senescence and inflammation and we discuss whether embryos reprogram the immune response.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064983","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":"Preeclampsia is associated with placental complement C4d deposition","authors":"E. Pierik ,&nbsp;M.H. de Jong-Schoots ,&nbsp;M. Bulthuis ,&nbsp;M.R. Daha ,&nbsp;J. van den Born ,&nbsp;S.J. Gordijn ,&nbsp;J.R. Prins","doi":"10.1016/j.placenta.2025.09.001","DOIUrl":"10.1016/j.placenta.2025.09.001","url":null,"abstract":"<div><h3>Introduction</h3><div>Preeclampsia complicating pregnancy can be life-threatening for both mother and infant, often resulting in maternal and neonatal morbidity. Previous studies have related changes in specific immune factors to preeclampsia; however, the role of the complement system in preeclampsia remains understudied. Therefore, this study aims to examine differences in placental complement deposition in pregnancies complicated by preeclampsia and healthy term control pregnancies. In addition, we compared early and late preeclampsia with healthy term and spontaneous preterm births.</div></div><div><h3>Methods</h3><div>Placentas from pregnancies complicated by early onset preeclampsia (n = 26), late onset preeclampsia (n = 26), healthy term controls (n = 24), and spontaneous preterm births (n = 14) were investigated for the presence of complement using immunohistochemistry for C1q, C4d, C3d, C5b-9, and CD59.</div></div><div><h3>Results</h3><div>Deposition of C4d was observed at the trophoblast in 25.5 % of all preeclampsia cases and differed from healthy term controls (p = 0.029). C4d was observed in 12.0 % of late onset preeclampsia and 38.5 % of early onset preeclampsia placentas. None or minimal C4d was found in placentas of healthy term and preterm births. C4d trophoblast deposition significantly differed between early onset preeclampsia and healthy term (p = 0.002) and spontaneous preterm births (p = 0.022). With respect to C1q, C3d, C5b-9 and CD59, no significant differences were observed between the groups.</div></div><div><h3>Conclusion</h3><div>Our data demonstrate an increase in C4d deposition in placentas of early onset preeclampsia compared to healthy term controls and spontaneous preterm births, suggesting a possible role for the complement system in preeclampsia. Our findings underscore the complexity of preeclampsia pathophysiology and highlight the need for more refined, subtype-specific investigations.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"171 ","pages":"Pages 45-51"},"PeriodicalIF":2.5,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086953","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":"Perturbation of the ovine placental transcriptome occurs at sub-therapeutic exposures to antenatal steroid therapy","authors":"Erin L. Johnson ,&nbsp;Haruo Usuda ,&nbsp;Sean W.D. Carter ,&nbsp;Hideyuki Ikeda ,&nbsp;Yusaku Kumagai ,&nbsp;Tsukasa Takahashi ,&nbsp;Yuki Takahashi ,&nbsp;Yuya Saito ,&nbsp;Hannah R.S. Watson ,&nbsp;Michael W. Clarke ,&nbsp;Demelza J. Ireland ,&nbsp;John P. Newnham ,&nbsp;Masatoshi Saito ,&nbsp;Sebastian E. Illanes ,&nbsp;Binny Priya Sesurajan ,&nbsp;Mahesh A. Choolani ,&nbsp;Alan H. Jobe ,&nbsp;Matthew W. Kemp","doi":"10.1016/j.placenta.2025.09.002","DOIUrl":"10.1016/j.placenta.2025.09.002","url":null,"abstract":"<div><h3>Introduction</h3><div>Antenatal steroid (ANS) therapy accelerates preterm lung maturation. Clinical and experimental data show current regimens disrupt placental function and transport and impact fetal growth. We have previously shown that higher materno-fetal steroid exposures increase fetal glucocorticoid clearance. Using a sheep model, we aimed to determine whether: (i) placental transcriptomic changes correlate with fetal glucocorticoid exposure; (ii) these changes persist below the threshold for lung maturation; and (iii) transcriptomic changes explain altered steroid clearance and fetal growth.</div></div><div><h3>Methods</h3><div>This secondary analysis included singleton fetuses delivered at 123 ± 1 days’ gestation (n = 6/group), ventilated for 30-min, then euthanized. Fetuses received a 48-h infusion targeting plasma betamethasone levels of 2, 1, or 0.5 ng/mL, a control group received saline. Placental tissue was collected for RNA sequencing, fetal liver for qPCR and betamethasone concentrations were measured by LCMS.</div></div><div><h3>Results</h3><div>Maximal lung maturation occurred at 2 ng/mL. Placental transcriptome changes were dose-dependent, with 2052, 408, and 498 differentially expressed genes in the 2, 1, and 0.5 ng/mL groups, respectively. KEGG analysis showed suppression of DNA replication, nucleocytoplasmic transport, and cell cycle (p &lt; 0.001), and activation of steroid hormone biosynthesis pathways, including upregulation of UGT1A4 and CYP17A1. Placental transporters SLC4A10, SLC7A3, SLC36A3, SLC46A1 and SLC6A3 were downregulated at 2 ng/mL. In the fetal liver, expression of transport protein ABCB1 increased across all treatment groups.</div></div><div><h3>Discussion</h3><div>Placental transcriptomic disruption persisted at and below the ANS exposure necessary for lung maturation. These findings suggest placental involvement in both impaired fetal growth and steroid clearance and underscore the need to optimize ANS dosing.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"171 ","pages":"Pages 1-15"},"PeriodicalIF":2.5,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144997491","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":"ASCT2-dependent secretion mechanism of the cell fusion-regulator suppressyn","authors":"Jun Sugimoto ,&nbsp;Danny J. Schust ,&nbsp;Takeshi Nagamatsu ,&nbsp;Yoshiki Kudo","doi":"10.1016/j.placenta.2025.07.018","DOIUrl":"10.1016/j.placenta.2025.07.018","url":null,"abstract":"","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"169 ","pages":"Page 135"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144996207","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":"Cholesterol sulfate prevents maternal-fetal conflict by locally modulating immune reactivity","authors":"Kenichiro Hirotani ,&nbsp;Kazufumi Kunimura ,&nbsp;Yoshinori Fukui ,&nbsp;Kiyoko Kato","doi":"10.1016/j.placenta.2025.07.034","DOIUrl":"10.1016/j.placenta.2025.07.034","url":null,"abstract":"","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"169 ","pages":"Page 140"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144996336","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":"Roles of G3BP1 and IFI6 in placenta against SARS-CoV-2 infection during the second trimester","authors":"Kazuhide Takada ,&nbsp;Yuichiro Hirata ,&nbsp;Ryo Maekawa ,&nbsp;Seiya Ozono ,&nbsp;Quang Duy Trinh ,&nbsp;Yoshinori Takeda ,&nbsp;Daisuke Tominaga ,&nbsp;Noriko M. Tsuji ,&nbsp;Hideto Yamada ,&nbsp;Yoshihiko Araki ,&nbsp;Tadaki Suzuki ,&nbsp;Satoshi Hayakawa ,&nbsp;Shihoko Komine-Aizawa","doi":"10.1016/j.placenta.2025.07.044","DOIUrl":"10.1016/j.placenta.2025.07.044","url":null,"abstract":"","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"169 ","pages":"Page 143"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144996463","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}