Placenta最新文献

{"title":"Extracellular matrix induces trophoblast HtrA4 expression: Implications for the pathogenesis of placenta accreta spectrum","authors":"Chie-Pein Chen ,&nbsp;Chen-Yu Chen ,&nbsp;Chia-Yu Chen ,&nbsp;Yi-Hsiu Kuo ,&nbsp;Hungwen Chen","doi":"10.1016/j.placenta.2025.04.028","DOIUrl":"10.1016/j.placenta.2025.04.028","url":null,"abstract":"<div><h3>Objective</h3><div>To study whether the upregulation of HtrA4 expression in extravillous trophoblasts and the downregulation of HtrA1 expression in defective deciduae underlined the mechanisms of placenta accreta spectrum (PAS) development.</div></div><div><h3>Methods</h3><div>Tissue samples from patients undergone cesarean hysterectomy because of postpartum hemorrhage due to PAS <em>(n = 15)</em> or uterine atony <em>(</em>control group; <em>n = 10) were</em> analyzed through immunostainings. The effect of extracellular matrix (ECM) on trophoblast HtrA4 expression, and HtrA4 in the alteration of trophoblast epithelial-to-mesenchymal transition, proliferation, invasion and HtrA1 inhibition were assessed.</div></div><div><h3>Results</h3><div>ECM molecule collagen I, collagen IV, fibronectin, or laminin were highly expressed in decidua and myometrium. Culturing trophoblasts with these molecules induced HtrA4 expression. HtrA4 upregulated the expression of N-cadherin, vimentin, integrin β1, snail, and matrix metalloproteinase-2 but downregulated that of zonula occludens-1. HtrA4 knockdown inhibited these effects. HtrA4 knockdown or pretreatment with recombinant HtrA1 inhibited HtrA4-induced trophoblast invasion. HtrA4 promoted trophoblast proliferation. Numerous extravillous trophoblasts exhibiting strong HtrA4 expression invaded the myometrium at the villous adherence sites affected by PAS. Relatively few extravillous trophoblasts were observed at the nonadherence sites and in the control specimens; these trophoblasts exhibited weak or no HtrA4 expression. HtrA1 was primarily expressed over the decidua.</div></div><div><h3>Discussion</h3><div>ECM in decidua and myometrium induced trophoblast HtrA4 expression. Decidual HtrA1 inhibited HtrA4-induced trophoblast invasion. Without the inhibition of HtrA1, HtrA4 expression and invasion was upregulated in the trophoblasts of patients with PAS. The reciprocal effects of HtrA4 and HtrA1 at the maternal-fetal interface may be involved in the pathogenesis of PAS.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"167 ","pages":"Pages 71-79"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143910967","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":"Inflammatory features in placentas of women with endometriosis and their relation to maternal and neonatal outcomes","authors":"Liat Mor ,&nbsp;Roni Goldenberg ,&nbsp;Ran Keidar ,&nbsp;Eliel Kedar Sade ,&nbsp;Letizia Schreiber ,&nbsp;Eran Weiner ,&nbsp;Elad Barber","doi":"10.1016/j.placenta.2025.04.019","DOIUrl":"10.1016/j.placenta.2025.04.019","url":null,"abstract":"<div><h3>Background</h3><div>Endometriosis, affecting 6–10 % of reproductive-age women, is linked to infertility and adverse pregnancy outcomes. Its association with immune dysregulation and potential role in pregnancy complications remain unclear. Placental histopathology can provide insight into intrauterine inflammatory processes. This study examines the relationship between endometriosis and placental pathology to explore mechanisms underlying adverse pregnancy outcomes.</div></div><div><h3>Methods</h3><div>A retrospective cohort study included patients with endometriosis (n = 50) and a matched control group without endometriosis (n = 150) who delivered singleton term pregnancies at a tertiary center (2008–2023). Maternal characteristics, pregnancy outcomes, and placental histopathology were compared.</div></div><div><h3>Results</h3><div>While maternal and pregnancy characteristics were similar, endometriosis was associated with higher rates of intrapartum fever (10 % vs. 2.6 %, p = 0.045) and placental abnormalities, including placental hemorrhage (10 % vs. 2.6 %, p = 0.045), maternal and fetal inflammatory response features (16 % vs. 6 %, p = 0.039, and 8 % vs. 1.3 %, p = 0.035 respectively), chronic villitis of unknown etiology (8 % vs. 1.3 %, p = 0.035), and chronic deciduitis (14 % vs. 2.6 %, p = 0.006). Composite adverse neonatal outcomes were significantly higher in the endometriosis group (16 % vs. 4 %, p = 0.007). Multivariable regression confirmed associations between endometriosis, inflammatory placental features, and adverse neonatal outcomes.</div></div><div><h3>Conclusions</h3><div>Endometriosis is linked to increased placental inflammatory features and higher adverse neonatal outcome rates. These findings highlight the need for enhanced surveillance and targeted interventions in pregnancies complicated by endometriosis.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"167 ","pages":"Pages 35-41"},"PeriodicalIF":3.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143895170","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":"Hyperglycemia-induced α-Klotho downregulation impairs mitophagy and promotes placental dysfunction in T2DM pregnancies","authors":"Jianhua Niu ,&nbsp;Bing Han ,&nbsp;Shuxian Wang ,&nbsp;Yumei Wei ,&nbsp;Zhe Liu ,&nbsp;Huixia Yang","doi":"10.1016/j.placenta.2025.04.024","DOIUrl":"10.1016/j.placenta.2025.04.024","url":null,"abstract":"<div><h3>Introduction</h3><div>Placental dysfunction in pregnancies complicated by type 2 diabetes mellitus (T2DM) is associated with adverse maternal and fetal outcomes. α-Klotho, a multifunctional anti-aging protein, plays a critical role in maintaining cellular homeostasis, but its role in T2DM-induced placental dysfunction remains poorly understood.</div></div><div><h3>Methods</h3><div>Placental tissues from T2DM pregnancies and normoglycemic controls were analyzed for α-Klotho expression using qRT-PCR, Western blot, and immunohistochemistry. BeWo trophoblast cells were cultured under normoglycemic and hyperglycemic conditions, with α-Klotho knockdown and overexpression to explore its regulatory effects. Transcriptomic analysis was conducted to identify affected pathways, and markers of mitophagy and reactive oxygen species (ROS) were analyzed.</div></div><div><h3>Results</h3><div>α-Klotho expression was significantly reduced in the placentas of T2DM pregnancies and in trophoblast cells under hyperglycemic conditions. Transcriptomic analysis identified pathways related to mitochondrial dysfunction and impaired mitophagy as key processes regulated by α-Klotho. Hyperglycemia and α-Klotho knockdown suppressed mitophagy, while ROS production was increased, further exacerbating oxidative stress. Overexpression of α-Klotho restored mitophagy and mitigated ROS activation.</div></div><div><h3>Discussion</h3><div>This study reveals that α-Klotho downregulation contributes to T2DM-induced placental dysfunction by impairing mitophagy and increasing oxidative stress. These findings provide new insights into the molecular mechanisms underlying placental abnormalities in diabetic pregnancies and highlight α-Klotho as a potential therapeutic target.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"167 ","pages":"Pages 95-103"},"PeriodicalIF":3.0,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931462","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":"First trimester extravillous trophoblast secretes HLA class I molecules via small extracellular vesicles","authors":"Marina Alexandrova ,&nbsp;Diana Manchorova ,&nbsp;Ivaylo Vangelov ,&nbsp;Antonia Terzieva ,&nbsp;Violeta Dimitrova ,&nbsp;Gil Mor ,&nbsp;Tanya Dimova","doi":"10.1016/j.placenta.2025.04.023","DOIUrl":"10.1016/j.placenta.2025.04.023","url":null,"abstract":"<div><h3>Introduction</h3><div>Human pregnancy requires acceptance and support for the semi-allogeneic embryo and effective protection of both mother and fetus. A failure to adapt, from either side, may cause abortion. The placenta-derived extracellular vesicles (EVs) have a crucial role in human implantation and pregnancy. These are lipid bilayer membrane-delimited, nano-to-micro sized extracellular microvesicles of endosomal origin, containing diverse signaling molecules, and functioning as short and long-distance messengers. We have already shown that first-trimester placenta releases the soluble HLA-C and HLA-G KIR ligands to modulate maternal cytotoxicity via the KIR/HLA axis. This study is to find whether extravillous trophoblast (EVT) secretes these HLA class I molecules via small EVs.</div></div><div><h3>Methods</h3><div>sEVs were isolated by ultrafiltration or precipitation from serum-free conditioned media from primary trophoblast-derived EVT, and non-tumor EVT-like model Sw71 cell line, cultured as monolayer and spheroids. sEVs from cultured placental explants served as a positive control. Combined data from several methods was used for their characterization including BCA, DLS, TEM, IEM, Dot blot, and FACS.</div></div><div><h3>Results</h3><div>Primary trophoblast-derived EVT and Sw71 EVT-like cells produced intact and well-visible CD63⁺, HLA-G- and HLA-C-bearing sEVs, regardless of culture mode and type of isolation. Both methods yielded sEVs sized 30–100 nm.</div></div><div><h3>Discussion</h3><div>We show original data on the HLA-C secretion via sEVs by early pregnancy EVT and confirm the production of HLA-G-positive sEVs. A new asset to the usefulness of the Sw71 spheroid model as an implanting blastocyst surrogate is added as a tool to elucidate the sEV-based signalization in the implantation.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"167 ","pages":"Pages 11-21"},"PeriodicalIF":3.0,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881800","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":"Impact of IVF-ET on obstetrics and perinatal outcomes in advanced maternal age women","authors":"Qian Li ,&nbsp;Xiaowei Wei ,&nbsp;Weihong Zeng ,&nbsp;Yi Lin","doi":"10.1016/j.placenta.2025.04.022","DOIUrl":"10.1016/j.placenta.2025.04.022","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the impact of in vitro fertilization and embryo transfer (IVF-ET) on pregnancy outcomes among women of advanced maternal age (AMA, ≥35 years), compared with spontaneous conceptions.</div></div><div><h3>Methods</h3><div>This retrospective cohort study analyzed 20,882 AMA singleton pregnancies (≥24 weeks) at a large tertiary maternity hospital in Shanghai, China. Outcomes were evaluated using stabilized IPTW-adjusted log-binomial regression and mediation analysis.</div></div><div><h3>Results</h3><div>IVF-ET was associated with increased risks of placental abnormalities (adjusted risk ratio (aRR) = 1.87, 95 % confidence interval (CI): 1.32–2.65), placental abruption (aRR = 1.68, 95 % CI: 1.33–2.13), placenta accreta (aRR = 2.52, 95 % CI: 1.34–4.72), placenta previa (aRR = 1.68, 95 % CI: 1.33–2.13), gestational diabetes mellitus (GDM, aRR = 1.30, 95 % CI: 1.16–1.45), preeclampsia (PE, aRR = 1.52, 95 % CI: 1.14–2.02), postpartum hemorrhage (aRR = 2.03, 95 % CI: 1.28–3.21), preterm birth (aRR = 1.31, 95 % CI: 1.04–1.64), cesarean section (CS, aRR = 1.19, 95 % CI: 1.13–1.24), neonatal asphyxia (aRR = 2.45, 95 % CI: 1.30–4.62), neonatal respiratory distress (aRR = 1.61, 95 % CI: 1.14–2.27), and neonatal jaundice (aRR = 1.36, 95 % CI: 1.09–1.70). Mediation analysis indicated that CS could explain 21.47 % and 26.15 % of IVF-ET's effect on postpartum hemorrhage and neonatal jaundice, respectively.</div></div><div><h3>Conclusion</h3><div>AMA women undergoing IVF-ET are associated with an elevated risk of abnormal placentation, PE, GDM and preterm birth. Higher CS rates mediate adverse neonatal outcomes and an increased risk of postpartum hemorrhage.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"167 ","pages":"Pages 55-62"},"PeriodicalIF":3.0,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903561","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":"Factors associated with the acquisition and retention of male-origin microchimerism in women","authors":"Tine Dreier Bille ,&nbsp;Laura Brasen Kidmose ,&nbsp;Cindy Melanie Krøyer ,&nbsp;Anne Tjønneland ,&nbsp;Mads Kamper-Jørgensen","doi":"10.1016/j.placenta.2025.04.021","DOIUrl":"10.1016/j.placenta.2025.04.021","url":null,"abstract":"<div><h3>Background</h3><div>Natural microchimerism is the presence of cells at low concentrations in one individual originating from another. Although most cells are cleared from the maternal vascular system shortly after delivery, microchimeric cells - presumably of fetal origin - can be detected in many women decades after pregnancy.</div></div><div><h3>Method</h3><div>This cross-sectional study includes 774 women who participated in the Danish Diet, Cancer, and Health cohort sampled from 1993 to 1997. We investigate sources of male-origin microchimerism related to childbearing in maternal peripheral blood and its association with lifestyle using logistic regression. Guided by previous reports, we distinguish between sources of acquisition and retention of male-origin microchimerism.</div></div><div><h3>Results</h3><div>Women who had given birth to a male fetus had significantly increased odds of testing positive for male-origin microchimerism compared with women who had never given birth to a male fetus (OR = 1.61, 95 % CI [1.12; 2.33]). Compared with current users of hormone replacement treatment, women who reported no or former use of hormone replacement treatment had increased odds of testing positive for male-origin microchimerism (OR = 1.57, 95 % CI [1.12; 2.21]; OR = 1.89, 95 % CI [1.14; 3.13]). Furthermore, women who reported having formerly smoked had increased odds of testing positive for male-origin microchimerism, compared with women who reported current smoking (OR = 1.77, 95 % CI [1.15; 2.75]).</div></div><div><h3>Conclusions</h3><div>We find that the acquisition of male-origin microchimerism is associated with pregnancy with a male fetus, and retention may be linked to external factors, including smoking.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"167 ","pages":"Pages 104-108"},"PeriodicalIF":3.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143937506","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":"Deep learning for fetal inflammatory response diagnosis in the umbilical cord","authors":"Marina A. Ayad ,&nbsp;Ramin Nateghi ,&nbsp;Abhishek Sharma ,&nbsp;Lawrence Chillrud ,&nbsp;Tilly Seesillapachai ,&nbsp;Teresa Chou ,&nbsp;Lee A.D. Cooper ,&nbsp;Jeffery A. Goldstein","doi":"10.1016/j.placenta.2025.04.013","DOIUrl":"10.1016/j.placenta.2025.04.013","url":null,"abstract":"<div><h3>Introduction</h3><div>Inflammation of the umbilical cord can be seen as a result of ascending intrauterine infection or other inflammatory stimuli. Acute fetal inflammatory response (FIR) is characterized by infiltration of the umbilical cord by fetal neutrophils, and can be associated with neonatal sepsis or fetal inflammatory response syndrome. Recent advances in deep learning in digital pathology have demonstrated favorable performance across a wide range of clinical tasks, such as diagnosis and prognosis. In this study we classified FIR from whole slide images (WSI).</div></div><div><h3>Methods</h3><div>We digitized 4100 histological slides of umbilical cord stained with hematoxylin and eosin (H&amp;E) and extracted placental diagnoses from the electronic health record. We build models using attention-based whole slide learning models. We compared strategies between features extracted by a model (ConvNeXtXLarge) pretrained on non-medical images (ImageNet), and one pretrained using histopathology images (UNI). We trained multiple iterations of each model and combined them into an ensemble.</div></div><div><h3>Results</h3><div>The predictions from the ensemble of models trained using UNI achieved an overall balanced accuracy of 0.836 on the test dataset. In comparison, the ensembled predictions using ConvNeXtXLarge had a lower balanced accuracy of 0.7209. Heatmaps generated from top accuracy model appropriately highlighted arteritis in cases of FIR 2. In FIR 1, the highest performing model assigned high attention to areas of activated-appearing stroma in Wharton's Jelly. However, other high-performing models assigned attention to umbilical vessels.</div></div><div><h3>Discussion</h3><div>We developed models for diagnosis of FIR from placental histology images, helping reduce interobserver variability among pathologists. Future work may examine the utility of these models for identifying infants at risk of systemic inflammatory response or early onset neonatal sepsis.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"167 ","pages":"Pages 1-10"},"PeriodicalIF":3.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143879033","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":"Significance of placental pathology and CMV PCR in assessing clinical outcomes of congenital CMV infection","authors":"Han Gyeol Kim ,&nbsp;Ji-Hee Sung ,&nbsp;Suk-Joo Choi ,&nbsp;Soo-young Oh ,&nbsp;Cheong-Rae Roh ,&nbsp;Yae-Jean Kim ,&nbsp;Yun Sil Chang ,&nbsp;Doo Ri Kim ,&nbsp;Il Joon Moon ,&nbsp;So Young Kang ,&nbsp;Jung-Sun Kim","doi":"10.1016/j.placenta.2025.04.020","DOIUrl":"10.1016/j.placenta.2025.04.020","url":null,"abstract":"<div><div>Congenital cytomegalovirus (CMV) infection is one of the most common congenital infections with adverse outcomes such as intrauterine growth restriction (IUGR), hearing loss, and neurologic deficits. The aim of this study was to investigate the significance of histopathologic features and CMV PCR results of placentas with clinical manifestation of congenital CMV infections.</div><div>We retrospectively collected the placentas of 27 newborns with congenital CMV infections from January 2009 to December 2020. Clinical information and placental histology were reviewed. Immunohistochemistry and PCR for CMV were performed with placental tissues.</div><div>Typical histological findings of CMV infection were detected in 18 placentas (66.7 %), including chronic villitis (66.7 %), plasma cell infiltration (29.6 %), viral inclusions (22.2 %), and hemosiderin (33.3 %). CMV was identified in 12 (44.4 %) cases by immunohistochemistry and 19 (70.4 %) cases by PCR. PCR detected CMV in 2 (22.2 %) out of 9 cases without CMV-typical histology. IUGR was more frequent in the CMV-typical histology group than in the no CMV-typical histology group (12/18 (66.7 %) vs 0/9 (0 %), <em>P</em> = 0.001) as well as in the PCR-positive CMV group than in the PCR-negative CMV group (11/19 (57.9 %) vs. 1/8 (12.5 %), <em>P</em> = 0.043). Hearing loss was associated with the presence of hemosiderin and calcification in placental villous tissues (6/7 (85.8 %) vs. 3/12 (25 %), <em>P</em> = 0.02, 7/7 (100 %) vs. 6/12 (50 %), <em>P</em> = 0.044).</div><div>The associations of placental pathologic findings and CMV PCR results with clinical outcomes of congenital CMV infection suggest that a comprehensive examination of the placenta is important in congenital CMV infection.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"167 ","pages":"Pages 22-27"},"PeriodicalIF":3.0,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890532","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":"Birth weight prediction using artificial intelligence-based placental assessment from macroscopic photo: a retrospective study","authors":"Yoo Jin Lee ,&nbsp;Mi-Young Lee ,&nbsp;Jin Hoon Chung ,&nbsp;Hye-Sung Won ,&nbsp;Bumwoo Park","doi":"10.1016/j.placenta.2025.04.018","DOIUrl":"10.1016/j.placenta.2025.04.018","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to predict newborn birth weight through multifactorial analysis of macroscopic placental images using artificial intelligence (AI).</div></div><div><h3>Methods</h3><div>We retrospectively reviewed the data of singleton pregnant women whose placentas were histopathologically examined at Asan Medical Center from January 2021 to December 2021. A total of 15 placental features were included in the machine learning using four regression analysis methods. Predictive performance matrics, including the mean absolute error (MAE), mean relative error (MRE), root mean square error (RMSE) and R² score, were calculated for each algorithm. The study population was divided into two groups according to placental pathological findings, which were subsequently compared.</div></div><div><h3>Results</h3><div>A total of 131 cases were included. For the machine learning analysis using all features, all 15 placental features were used. The second analysis using univariate predictive features was performed by excluding five features whose correlation values with birth weight were &lt;0.5. Using AI, a predictive algorithm was developed, with a minimum MAE of 257.72 g, MRE of 0.15, RMSE of 338.42 g and a maximum R² score of 0.77. The group with non-pathologic placentas showed a higher overall predictive performance than that with pathological placentas. Subanalysis of the machine learning model, excluding the placental weight, showed similar trends.</div></div><div><h3>Conclusions</h3><div>The AI algorithm developed using machine learning for multifactorial analysis of the placenta can be used for neonatal birth weight prediction. This algorithm might assist in estimating fetal growth if it can potentially be adapted for prenatal ultrasonography by analyzing changes in placental measurements.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"167 ","pages":"Pages 28-34"},"PeriodicalIF":3.0,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890533","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":"ULK2 deficiency stratifies autophagy-driven molecular subtypes and exacerbates trophoblasts apoptosis in preeclampsia","authors":"Jianfeng Gan ,&nbsp;Wenhan Zhou ,&nbsp;Huanqiang Zhao ,&nbsp;Jiejie Shao ,&nbsp;Yutong Cui ,&nbsp;Suwen Wu ,&nbsp;Huangfang Xu ,&nbsp;Yinan Wang ,&nbsp;Qiongjie Zhou ,&nbsp;Xiaotian Li","doi":"10.1016/j.placenta.2025.04.015","DOIUrl":"10.1016/j.placenta.2025.04.015","url":null,"abstract":"<div><h3>Introduction</h3><div>Preeclampsia (PE), a placenta-originated hypertensive disorder of pregnancy, lacks targeted therapies despite its significant contribution to maternal and fetal morbidity. Emerging evidence implicates autophagy dysregulation in PE pathogenesis, though its molecular heterogeneity remains unexplored. This study aims to investigate autophagy-related molecular subtypes in PE and identify ULK2 key regulators linking autophagic imbalance to placental dysfunction.</div></div><div><h3>Methods</h3><div>Placental transcriptomic datasets were analyzed to identify autophagy-related differentially expressed genes (ARGs). Unsupervised consensus clustering stratified 80 PE patients into molecular subtypes. Protein-protein interaction (PPI) networks, machine learning algorithms, and functional enrichment analyses were employed to delineate hub genes and pathways. ULK2's role was validated via qRT-PCR, shRNA knockdown in HTR8/SVneo trophoblasts, and immunofluorescence. A murine PE model was established using the ULK1/2 inhibitor MRT68921 to assess systolic blood pressure, fetal growth, and placental autophagy-apoptosis dynamics.</div></div><div><h3>Results</h3><div>Unsupervised clustering of 45 ARGs classified PE patients into <em>ULK2</em>^low and <em>ULK2</em>^high subtypes. The <em>ULK2</em>^low subtype exhibited severe clinical features: elevated preterm delivery, systolic hypertension, HELLP syndrome incidence and increased proteinuria. ULK2-kncokdown trophoblasts showed impaired autophagy and upregulated apoptosis. Six hub genes correlated with disease severity and inversely with ULK2 expression. In mice, ULK2 inhibition induced PE-like phenotypes: sustained hypertension, fetal growth restriction and severe proteinuria.</div></div><div><h3>Discussion</h3><div>ULK2 deficiency disrupts trophoblast homeostasis, driving placental dysfunction and severe clinical outcomes. The <em>ULK2</em>^low subtype highlights autophagy heterogeneity in PE. While pharmacological ULK2 inhibition recapitulates PE in mice, limitations include sample size and MRT68921's dual ULK1/2 activity. Our findings propose ULK2 agonism as novel therapeutic strategies.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"167 ","pages":"Pages 42-54"},"PeriodicalIF":3.0,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901976","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}