Placenta最新文献

{"title":"Increased DNA damage/repair response in placentas from women infected with COVID-19 in pregnancy","authors":"Yang Gu ,&nbsp;Jie Xu ,&nbsp;Xin Gu ,&nbsp;Xiaohong Lu ,&nbsp;David F. Lewis ,&nbsp;Rona S. Scott ,&nbsp;Dani Zoorob ,&nbsp;Yuping Wang","doi":"10.1016/j.placenta.2025.05.009","DOIUrl":"10.1016/j.placenta.2025.05.009","url":null,"abstract":"<div><h3>Introduction</h3><div>SARS-CoV-2 may induce DNA damage in infected cells. The objective of the study is to determine if maternal COVID-19 infection can induce cellular DNA damage in the placenta. We examined phospho-Histone H2AX (pH2AX) foci-positive cells, MRE11 expression, and telomere length (markers of DNA damage/repair) in placental specimens from women with or without COVID-19 infection during pregnancy.</div></div><div><h3>Methods</h3><div>A total of 61 placental formalin-fixed paraffin embedded (FFPE) tissue specimens were used in the study, 33 in the COVID-19 group and 28 in the control group. Expression of pH2AX (Ser-139) and MRE11 was determined by immunostaining. Telomere length was assessed using the relative Human Telomere Length Quantification qPCR Assay Kit. Maternal demographic data was obtained via electronic medical record review. Data were analyzed by unpaired <em>t</em>-test or Chi-square test. A p level &lt;0.05 was set statistically significant.</div></div><div><h3>Results</h3><div>pH2AX foci-positive cells in the placentas were significantly higher in the COVID group than in the control group, p &lt; 0.01; Relative expression of MRE11 was significantly increased in the COVID group (15.68 ± 1.57) than in the control group (5.74 ± 1.21), p &lt; 0.01. In contrast, relative telomere length was significantly shorter in the COVID group (0.839 ± 0.123) than in the control group (1.652 ± 0.285), p &lt; 0.05. The correlation of telomere length with placental weight and gestational age at delivery and the correlation of placental/newborn ratio were also analyzed.</div></div><div><h3>Conclusions</h3><div>Both pH2AX and MRE11 are biomarkers of DNA double-strand breaks. Telomeres are targets of a persistent DNA damage response, and reduced telomere length is an indicator of cellular senescence and aging. Our findings of increased pH2AX foci-positive cells and MRE11 expression and reduced telomere length in placental cells from women infected with COVID-19 in pregnancy provide plausible evidence that increased placental cellular DNA damage could be associated with maternal COVID-19 infection in pregnancy.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"167 ","pages":"Pages 152-160"},"PeriodicalIF":3.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090724","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 weight in pregnancies complicated by fetal congenital heart defects","authors":"Jarmila A. Zdanowicz ,&nbsp;Sophie von Dach ,&nbsp;Ann-Kristin Justen ,&nbsp;Flavia Pagano ,&nbsp;Céline Smaadahl ,&nbsp;Daniel Surbek ,&nbsp;Martin Gloeckler ,&nbsp;Luigi Raio","doi":"10.1016/j.placenta.2025.05.010","DOIUrl":"10.1016/j.placenta.2025.05.010","url":null,"abstract":"<div><h3>Introduction</h3><div>Congenital heart defects (CHD) are the most common malformations. Fetuses with CHD are at an increased risk of being born small for gestational age (SGA), suggesting an impaired placental function. Our aim was to investigate the interdependence between fetal heart and placenta in pregnancies affected by isolated CHD.</div></div><div><h3>Methods</h3><div>This was a retrospective cohort study at a tertiary referral center. All singleton pregnancies with suspected fetal CHD between 2009 and 2020 were included. Confirmed CHD were allocated to one of six subgroups according to neonatal echocardiography or autopsy. Birth weight (b), placental weight (p), b/p ratio were calculated and compared between the subgroups, respectively.</div></div><div><h3>Results</h3><div>302 fetuses with confirmed CHD were analyzed. The overall incidence of SGA neonates with isolated CHD was 33/161 (20.4 %), while 28.4 % (38/134) of CHD placental weights were below the 10th percentile, with the highest incidence in cases with isolated univentricular (42.9 %) and left-sided (37.1 %) cardiac lesions. Mean b/p ratio in isolated cases was 5.32 (SD ± 1.51), and 23/134 (17.2 %) were &gt; 90th percentile. 11/302 (3.6 %) of pregnancies were affected by preeclampsia. All neonates were SGA and 7/10 (70 %) placental weights were &lt; 10th percentile.</div></div><div><h3>Conclusion</h3><div>The incidence of small placentas, SGA and preeclampsia is increased in pregnancies with fetal CHD. Disturbances in fetal cardio-placental hemodynamics may alter the development of the villous tree resulting in small placentas and fetuses, suggesting a second hit on the placenta, particularly in preeclampsia. Pregnancies with fetal CHD should be followed more closely for placental dysfunction and impaired fetal growth.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"167 ","pages":"Pages 166-174"},"PeriodicalIF":3.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099142","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":"The S100A11-RAGE/TLR4 axis activation mediates inflammatory response and epithelial integrity against Toxoplasma gondii infection in a human placental explant model","authors":"Jesús Guerrero-Muñoz MSc ,&nbsp;Ana Liempi PhD ,&nbsp;Alejandro Fernández-Moya MSc ,&nbsp;Sebastián Araneda-Rojas PhD ,&nbsp;Catalina Mendoza ,&nbsp;Francisca Seguy ,&nbsp;Gabriela Cáceres-Rojas MSc ,&nbsp;María Alejandra Gleisner PhD ,&nbsp;Ulrike Kemmerling PhD ,&nbsp;Christian Castillo PhD","doi":"10.1016/j.placenta.2025.05.008","DOIUrl":"10.1016/j.placenta.2025.05.008","url":null,"abstract":"<div><h3>Introduction</h3><div><em>Toxoplasma gondii</em> is a common zoonotic parasite that can cause serious congenital complications, such as neurological and ophthalmological disorders. While the placenta protects the fetus from pathogens, the immune response mechanisms to T. gondii are not well understood. This study focuses on how the infection affects the secretion of the host damage-associated molecular pattern S100A11, the activation of receptors RAGE and TLR4, and their role in maintaining placental barrier integrity and cytokine response against infection.</div></div><div><h3>Methods</h3><div>Human placental explants (HPEs) were challenged with <em>T. gondii</em> tachyzoites or LPS as a positive control in the presence and absence of specific inhibitors for RAGE (FPS-ZM1) and TLR4 (TAK-242). Expression of both PRRs was assayed by Western blot, RT-qPCR, and immunohistochemistry; placental damage was studied by standard histopathological methods (Hematoxylin-Eosin and Masson's Trichrome stain), expression of intercellular adhesion proteins Occludin and E-cadherin was analyzed by immunohistochemistry, the secreted DAMPs profiles by ELISA and cytokines by multiplex bead array.</div></div><div><h3>Results</h3><div><em>T. gondii</em> infection induces the secretion and expression of S100A11 and its receptor RAGE. Inhibition of RAGE does not reduce <em>T. gondii</em> infection. Interestingly, simultaneous inhibition of RAGE and TLR4 decreases the parasite-induced histopathological damage of the placental barrier, intercellular proteins E-cadherin and Occludin expression, and parasite load. In addition, the secretion of IL-8, and TNF were modulated by RAGE and TLR4 inhibition.</div></div><div><h3>Conclusion</h3><div>These results suggest that S100A11-RAGE/TLR4 axis activation is a significant mediator of the local placental immune response against <em>T. gondii</em>.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"167 ","pages":"Pages 131-139"},"PeriodicalIF":3.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143947636","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 Privilege: Evidence of organ resilience in severe COVID-19 in pregnancy.","authors":"Pietro Presicce, Marco Morselli, Anhyo Jeong, Marie Altendahl, Guadalupe Martinez, Giorgia Del Vecchio, Sherin U Devaskar, Matteo Pellegrini, Yalda Afshar, Suhas G Kallapur","doi":"10.1016/j.placenta.2025.05.003","DOIUrl":"https://doi.org/10.1016/j.placenta.2025.05.003","url":null,"abstract":"<p><strong>Background: </strong>COVID-19 infection in pregnancy is associated with preterm birth and an increased risk of severe disease, needing intensive care admission for management of maternal multi-organ failure. The placenta, a fetal organ, functions as a barrier at the maternal interface and expresses the SARS-CoV-2 viral receptors. However, placental infection and transplacental transfer of virus are rare, suggesting placental resistance to viral infection. Here, we seek to determine the impact of severe COVID-19 infection on maternal, newborn, and placental outcomes.</p><p><strong>Methods: </strong>A prospectively recruited cohort of pregnant COVID-19 patients (n = 204) at a quaternary perinatal academic center were retrospectively analyzed. During pregnancy umbilical artery (UA) Doppler assessment was performed to assess placental function. At delivery, maternal and fetal outcomes were assessed, with paired maternal peripheral blood and placenta samples collected (n = 26) for bulk RNA sequencing (RNA-seq). Post-sequencing analysis with single cell deconvolution and pathway analysis was performed.</p><p><strong>Results: </strong>Maternally-indicated preterm births were more frequent in severe, but not asymptomatic or mild/moderate COVID-19 infection. In severe COVID-19 infection, UA Doppler assessment was normal. Rates of fetal growth restriction and placenta:birth weight ratios were similar between groups. RNA-seq showed a distinct adaptive immune activation signature in peripheral blood while placental transcripts showed no significant changes in immune cell types.</p><p><strong>Conclusion: </strong>Despite multi-organ failure, severe COVID-19 did not significantly impact placental function and transcriptomics with iatrogenic preterm birth indicated for maternal-indications.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094559","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":"Increased locomotor activity does not mitigate the effects of advanced maternal age in a mouse model","authors":"Maria Elisa Osorio Nieto ,&nbsp;Jess C. Hercus ,&nbsp;Keilan R. Williams ,&nbsp;Daniel Alejandro Salcedo Rubio ,&nbsp;Caitlin D.M. Spreeuw ,&nbsp;Cheayeong Keum ,&nbsp;Julian K. Christians","doi":"10.1016/j.placenta.2025.05.007","DOIUrl":"10.1016/j.placenta.2025.05.007","url":null,"abstract":"<div><h3>Introduction</h3><div>Advanced maternal age (AMA) increases the risk of pregnancy complications, in part due to impaired placentation. While exercise during pregnancy can improve outcomes, its potential to mitigate the effects of AMA has not been investigated. We evaluated the impact of exercise in a mouse model of AMA.</div></div><div><h3>Methods</h3><div>Females were paired with males at 9 or 34 weeks of age, with one group of aged females having access to running wheels four weeks prior to and during pregnancy. Pregnant females (N = 19 per group) were collected at gestational day (GD) 11.5. Placentas were collected for RNA sequencing (N = 17–20 per group).</div></div><div><h3>Results</h3><div>Aged females with access to running wheels had lighter fat depots (1.0 ± 0.1 g) than those without (2.2 ± 0.1 g; p &lt; 0.0001), but did not differ from young females (0.8 ± 0.1 g; p = 0.5). Both groups of aged females had fewer viable conceptuses (without wheels: 4.0 ± 0.5, with wheels: 4.3 ± 0.5) than young mice (8.3 ± 0.5; p &lt; 0.0001 for both comparisons). Fetal crown-rump length was also lower in aged females (without wheels: 5.7 ± 0.2 mm, with wheels: 5.5 ± 0.2 mm, young: 6.6 ± 0.2 mm; p &lt; 0.0001 for both comparisons). Placental expression of only one gene was affected by access to running wheels, but 423 and 967 genes were differentially expressed between young and aged females without and with access to wheels, respectively. Placental transcriptomes suggested delayed placental development in aged females.</div></div><div><h3>Conclusions</h3><div>Our model reproduced previously-reported effects of age on fetal development and placental transcriptomics, but these were not mitigated by increased voluntary locomotor activity, despite a reduction in adiposity. Remarkably, increased voluntary locomotor activity had almost no effects on placental gene expression in aged mice.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"167 ","pages":"Pages 122-130"},"PeriodicalIF":3.0,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143947065","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":"Molecular insights into the corin function at the uteroplacental interface.","authors":"Ningzheng Dong, Meirong Du, Qingyu Wu","doi":"10.1016/j.placenta.2025.05.006","DOIUrl":"https://doi.org/10.1016/j.placenta.2025.05.006","url":null,"abstract":"<p><p>In pregnancy, cell-cell interactions and tissue remodeling are important physiological processes at the uteroplacental interface. To date, molecular mechanisms governing cell activities at the uteroplacental interface are not fully understood. Corin is a proteolytic enzyme responsible for activating atrial natriuretic peptide (ANP), a multifunctional hormone essential for cardiovascular and metabolic homeostasis. Upon progesterone stimulation, corin expression is induced in the uterus via a specific set of transcription factors. Uterine corin activates ANP to enhance decidualization and cell-cell interactions within the vasculature, leading to sequential vascular smooth muscle and endothelial cell death in spiral arteries. These events are crucial for uterine vascular remodeling and trophoblast invasion. Corin also functions in the decidua to regulate macrophage distribution and function in response to placental ischemia. In mice, Corin knockout impairs endometrial decidualization, vascular remodeling, and macrophage function at the uteroplacental interface, causing a preeclampsia (PE)-like phenotype. In humans, deleterious variants and impaired epigenetic modifications in the CORIN gene have been reported in women with PE, indicating that corin deficiency may be a contributing factor in the pathogenesis of PE. In this review, we describe the corin function at the uteroplacental interface and underlying molecular mechanisms. We also discuss potential implications of corin deficiency in pregnancy-associated diseases.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028225","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":"Maternal serum heparan sulfate in preeclampsia pathophysiology: Insights from a systematic review and meta-analysis.","authors":"Alejandra María Gómez-Gutiérrez, Angela María Alvarez-Gómez, Juan Carlos Quintana-Castillo, Julio Cesar Bueno-Sánchez, Walter D Cardona Maya","doi":"10.1016/j.placenta.2025.04.026","DOIUrl":"https://doi.org/10.1016/j.placenta.2025.04.026","url":null,"abstract":"<p><p>Preeclampsia (PE) is a hypertensive disorder that generally occurs after the first half of pregnancy, at delivery or even postpartum; it is associated with maternal organ dysfunction and significantly increases maternal, fetal, and newborn morbidity and mortality. During PE, the syncytiotrophoblast and endothelial cells are damaged, and molecules from the extracellular matrix, such as heparan sulfate (HS), can be released into the blood. Therefore, this study aimed to perform a systematic review and meta-analysis to assess the HS levels in serum from women with preeclampsia and normal pregnancy. To perform this systematic review and meta-analysis study, we comprehensively searched PubMed, ScienceDirect and LILACS and collected published studies about HS and preeclampsia. The risk of bias was assessed using the Newcastle-Ottawa Scale score. Upon search completion, 568 studies were identified, and 4 studies were retrieved for the present analysis. The forest plot showed an increase in serum HS in women with preeclampsia relative to non-preeclamptic women, standardized mean diference -SMD-with 95 % CI 1.2 (-0.41 to 2.81), and this relationship is maintained in early PE group (SMD 1.05; 95 % CI (0.22-2.32)). In conclusión, we presented here that HS possibly plays a vital role in the pathogenesis of preeclampsia since the results showed an increase in this molecule's levels in serum from women with preeclampsia.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120659","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":"Macrophage at maternal-fetal Interface: Perspective on pregnancy and related disorders.","authors":"Haoran Duan, Weinan Deng, Julia Kzhyshkowska, Dunjin Chen, Shuang Zhang","doi":"10.1016/j.placenta.2025.05.005","DOIUrl":"https://doi.org/10.1016/j.placenta.2025.05.005","url":null,"abstract":"<p><p>Immune cells at the maternal-fetal interface (MFI) undergo dynamic changes to facilitate fetal growth and development during pregnancy. In contrast to the adaptive immune system, where effector T cells, Tregs, and suppressor T cells play key roles in maintaining immune tolerance toward the semi-allogeneic fetus, the innate immune system-comprising decidual nature killer (dNK) cells, macrophages, and dendritic cells (DCs)-makes up a significant portion of the decidual leukocyte population. These innate immune cells are crucial in modulating trophoblast invasion, spiral artery remodeling, and apoptotic cell phagocytosis. Dysregulation of the innate immune system has been linked to impaired uterine vessel remodeling and defective trophoblast invasion, which can lead to complications such as spontaneous abortion, preeclampsia (PE), and preterm. This review focuses on recent advancements in understanding the innate immune defenses at the maternal-fetal interface and their connections to pregnancy-related diseases, with particular emphasis on the role of macrophages.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120656","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":"Recent advances in multimodal approaches for investigating placental development and related diseases.","authors":"Hao Wang, Tao Zhang, Jing Ruan, Xi Zheng, Shuwei Zheng, Qiqi Liu, Fen He, Bo Sun, Qi Zhang, Yuanfang Zhu, Xiaoyan Chen","doi":"10.1016/j.placenta.2025.05.004","DOIUrl":"https://doi.org/10.1016/j.placenta.2025.05.004","url":null,"abstract":"<p><p>The placenta is a vital organ that supports fetal growth and pregnancy maintenance. Its dysfunction is associated with severe complications, including preeclampsia, fetal growth restriction, and placenta accreta spectrum disorders. Traditional approaches to placental research have provided valuable insights but are limited in capturing the complexity of this dynamic organ. In recent years, multimodal approaches-integrating advanced imaging, single-cell and spatial omics, and artificial intelligence (AI)-have enabled comprehensive analyses of placental development and disease. These strategies offer improved diagnostic accuracy, deeper molecular understanding, and real-time assessment of placental function. This review summarizes recent advances in multimodal placental research, highlighting key technologies such as ultrasound and MRI, single-cell transcriptomics, spatial profiling, and AI-based prediction models. Particular emphasis is placed on contributions from Chinese research teams, who have developed novel platforms, atlases, and clinically relevant tools. We also discuss ongoing challenges, including data standardization, interpretability of AI models, and ethical considerations. Looking ahead, the integration of multimodal data with AI and wearable technologies holds promise for precision obstetrics and individualized pregnancy care. Together, these innovations are advancing both scientific understanding and clinical management of placenta-related disorders.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079868","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":"Cytotoxicity and induction of proinflammatory cytokines in placental explant cells following azathioprine exposure.","authors":"Franciele Rodrigues Araújo, Adriana Lopes da Silva, Leandro de Oliveira, Simone Correa-Silva, Estela Bevilacqua","doi":"10.1016/j.placenta.2025.05.002","DOIUrl":"https://doi.org/10.1016/j.placenta.2025.05.002","url":null,"abstract":"<p><p>Immunosuppressive drugs offer hope for the survival and motherhood of women with various disorders. Although the systemic side effects of these drugs on mothers have been studied, their impact on the placenta remains poorly understood, which can negatively affect fetal and postnatal development. This study investigated the effects of Azathioprine, an immunosuppressive drug, on the chorionic villi of human placentas from healthy pregnancies, focusing on cellular vitality and pro-inflammatory cytokines expression. Chorionic villi from term placentas were cultured and treated with Azathioprine at concentrations ranging from 0 to 100 ng/mL for 24 h. Azathioprine reduced mitochondrial metabolic activity (MTT assay) at all concentrations tested (p < 0.05) and increased cellular injury rates (LDH assay) at 50 and 100 ng/mL (p < 0.05). It also elevated protein (at 12.5 and 25 ng/mL, p < 0.05) and gene expression levels of interleukin (IL)-1β (12.5 ng/mL, p < 0.05). Protein levels of IL-18 increased significantly following Azathioprine exposure (p < 0.05), along with cleaved Caspase-1 (p = 0.003) and phosphorylated NF-κB levels (p < 0.05), compared to controls. IL-18 gene expression was elevated only at 12.5 ng/mL (p < 0.0005). These findings suggest that Azathioprine creates a cytotoxic microenvironment that disrupts the metabolism of chorionic villi, leading to injury and activation of pro-inflammatory cytokine expression. Such changes may contribute to an imbalance in placental homeostasis, potentially associated with adverse maternal and neonatal outcomes that warrant further investigation.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143394","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}