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Priority Setting Partnership on Placental Pathology: Consensus recommendations for placental research 优先设置伙伴关系在胎盘病理学:共识建议胎盘研究。
IF 3 2区 医学 Q2 DEVELOPMENTAL BIOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.placenta.2024.12.020
Mauritia C. Marijnen , M.I. Bügel , T. Yee Khong , Neil J. Sebire , Alexander E.P. Heazell , Wessel Ganzevoort , Frank H. Bloomfield , Elisabeth M.W. Kooi , Lotte-Elisabeth van der Meeren , Sanne J. Gordijn

Introduction

The placenta supports the metabolic and respiratory requirements of the fetus. Placental disorders, caused by various pathophysiological mechanisms, may result in adverse pregnancy and neonatal outcomes. Knowledge gaps remain in the understanding, reporting and interpretation of placental pathology relating to clinical conditions. This project aimed to collaboratively identify the most important unanswered research questions related to placental pathology.

Methods

An international Priority Setting Partnership (PSP) was conducted, involving (perinatal) pathologists, obstetricians, paediatrician-neonatologists, midwives, and scientists with expertise in placental pathology. In the first survey, participants identified their three most important unanswered research questions. Afterwards literature was reviewed for evidence on the proposed questions. In a second survey, participants ranked the most important questions from an initial long-list. The top-ranked questions were then discussed and finalized in a 1-h online consensus workshop.

Results

Ninety participants completed the first survey. The majority of stakeholders were perinatal pathologists (n = 39 (43.3 %) and most were based in Europe (n = 43 (47.8 %). 270 questions were submitted; after review, these were subdivided into 32 overarching questions. The second ranking survey was completed by 53 participants. Twenty-five participants attended the online workshop, which reached consensus on the top 10. The questions focus, among others, on causes, recurrence risk, consistency of reporting, diagnosing tools and potential use of artificial intelligence.

Discussion

Following this international PSP, the top 10 prioritized research questions on placental pathology have been identified. This will inform the research agenda for funders and policy-makers, and is intended to improve care for patients suffering from placental insufficiency.
胎盘支持胎儿的代谢和呼吸需求。由各种病理生理机制引起的胎盘疾病可能导致不良的妊娠和新生儿结局。知识差距仍然存在的理解,报告和解释胎盘病理相关的临床条件。该项目旨在共同确定与胎盘病理学相关的最重要的未解研究问题。方法:开展了一项国际重点确定伙伴关系(PSP),涉及(围产期)病理学家、产科医生、儿科-新生儿医生、助产士和胎盘病理学专家。在第一次调查中,参与者确定了他们最重要的三个未回答的研究问题。随后,对文献进行了回顾,以寻找有关所提问题的证据。在第二项调查中,参与者从最初的一长串问题中选出最重要的问题。然后在1小时的在线共识研讨会上讨论并最终确定排名靠前的问题。结果:90名参与者完成了第一次调查。大多数利益相关者是围产期病理学家(n = 39(43.3%)),大多数来自欧洲(n = 43(47.8%))。共提交问题270个;经过审查,这些问题被细分为32个总体问题。第二项排名调查由53名参与者完成。25名参与者参加了在线研讨会,并就前10名达成了共识。这些问题主要集中在原因、复发风险、报告的一致性、诊断工具和人工智能的潜在应用等方面。讨论:在本次国际PSP之后,确定了胎盘病理学的十大优先研究问题。这将为资助者和决策者的研究议程提供信息,并旨在改善对胎盘功能不全患者的护理。
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引用次数: 0
Profiling epithelial viral receptor expression in amniotic membrane and nasal epithelial cells at birth 出生时羊膜和鼻上皮细胞上皮病毒受体表达谱分析。
IF 3 2区 医学 Q2 DEVELOPMENTAL BIOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.placenta.2024.12.029
Bailee Renouf , Erika N. Sutanto , Courtney Kidd , James Lim , Minda Amin , Luke Berry , Gerard F. Hoyne , Nina D'Vaz , Elizabeth Kicic-Starcevich , Stephen M. Stick , Thomas Iosifidis , the AERIAL study team

Introduction

Children with wheeze and asthma present with airway epithelial vulnerabilities, such as impaired responses to viral infection. It is postulated that the in utero environment may contribute to the development of airway epithelial vulnerabilities. The aims of the study were to establish whether the receptors for rhinovirus (RV), respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are expressed in the amniotic membrane and whether the pattern of expression is similar to newborn nasal epithelium.

Methods

Placenta were collected (n = 33) from newborns in AERIAL, a sub-study nested under the ORIGINS birth cohort. Using purified RNA from amniotic samples (n = 33), along with previously extracted RNA from nasal epithelial cells from newborns (n = 20), real-time quantitative polymerase chain reaction (qPCR) was performed to determine gene expression of viral receptors for RV, RSV and SARS-CoV-2 in both amniotic and newborn nasal epithelial samples. In addition, receptor protein expression was quantified through Western blot and localised using immunohistochemical staining in amniotic samples.

Results

Amniotic and newborn nasal samples expressed various receptors for RV (ICAM-1, LDLR, CDHR3), RSV (NCL, CX3CR1) and SARS-CoV-2 (ACE2, TMPRSS2) at the gene level, although the magnitude of expression varied. In addition, protein expression of these receptors was confirmed in the amniotic samples. These proteins were localised to the epithelial layer of the amniotic membrane.

Conclusion

This proof-of-concept study indicates the potential of amniotic samples to facilitate investigation into the interactions between the in utero environment and prenatal programming of epithelial innate immune responses to viruses.
患有喘息和哮喘的儿童存在气道上皮脆弱性,例如对病毒感染的反应受损。据推测,子宫内环境可能有助于气道上皮易感性的发展。本研究的目的是确定鼻病毒(RV)、呼吸道合胞病毒(RSV)和严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)受体是否在羊膜中表达,其表达模式是否与新生儿鼻上皮相似。方法:在ORIGINS出生队列的子研究AERIAL中收集新生儿胎盘(n = 33)。利用羊膜样本纯化的RNA (n = 33),以及先前从新生儿鼻上皮细胞中提取的RNA (n = 20),采用实时定量聚合酶链反应(qPCR)检测羊膜和新生儿鼻上皮样本中RV、RSV和SARS-CoV-2病毒受体的基因表达。此外,通过Western blot定量羊膜样品中的受体蛋白表达,并使用免疫组织化学染色进行定位。结果:羊水和新生儿鼻腔样本在基因水平上表达了不同的RV受体(ICAM-1、LDLR、CDHR3)、RSV受体(NCL、CX3CR1)和SARS-CoV-2受体(ACE2、TMPRSS2),但表达量不同。此外,这些受体的蛋白表达在羊膜样品中得到证实。这些蛋白定位于羊膜上皮。结论:这项概念验证性研究表明,羊水样本可能有助于研究子宫内环境与上皮细胞对病毒的先天免疫反应的产前编程之间的相互作用。
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引用次数: 0
Sex-specific associations between feto-placental growth and maternal physical activity volume and sitting time: Findings from the Queensland Family Cohort study 胎儿胎盘生长与母亲体力活动量和静坐时间之间的性别特异性关联:来自昆士兰家庭队列研究的发现。
IF 3 2区 医学 Q2 DEVELOPMENTAL BIOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.placenta.2024.12.027
Jade M. Kubler , Kassia S. Beetham , Sarah E. Steane , Olivia J. Holland , Danielle J. Borg , Kym M. Rae , Sailesh Kumar , Vicki L. Clifton

Introduction

Antenatal physical activity (PA) is associated with beneficial changes in placental growth and function; however, the effect of excessive sitting time is less clear. The aim of this study was to investigate whether feto-placental growth changes with maternal activity, and whether these associations differ in a sex-specific manner.

Methods

This study included women enrolled in the Queensland Family Cohort study who self-reported PA and sitting time at 24 or 36 weeks of gestation. Placental growth factors and feto-placental growth parameters at delivery were analysed by PA volume and sitting time, as well as by fetal sex.

Results

Women who reported excessive sitting time during mid-pregnancy and had a female fetus showed higher placental PlGF (p = 0.031) and FLT1 (p = 0.032) mRNA expression with no difference in placental size at delivery. For the male, excessive sitting time during mid-pregnancy was associated with a lower placental weight (p = 0.001) and placental surface area (p = 0.012) and a higher birthweight to placental weight (BWPW) ratio (p = 0.042), with no change in placental growth factors. Moderate volume PA during mid-pregnancy was associated with lower VEGFA mRNA expression in the male placenta (p = 0.005) and a higher abdominal circumference in the female neonate (p = 0.042), with no overall difference in placental weight or birthweight for either sex.

Conclusions

The results of this study suggest that mid-pregnancy may be an important timepoint for programming of feto-placental growth in relation to maternal activity. Our findings highlight the independent benefits of reducing sitting time during pregnancy, particularly for women carrying male fetuses.
产前体育活动(PA)与胎盘生长和功能的有益变化有关;然而,久坐的影响还不太清楚。本研究的目的是调查胎儿胎盘生长是否随母体活动而改变,以及这些关联是否以性别特异性的方式不同。方法:本研究包括参加昆士兰家庭队列研究的妇女,她们在妊娠24或36周时自我报告PA和坐着时间。分娩时胎盘生长因子和胎儿胎盘生长参数通过胎心容积、坐位时间以及胎儿性别进行分析。结果:怀孕中期坐着时间过长的女性胎儿胎盘PlGF (p = 0.031)和FLT1 (p = 0.032) mRNA表达较高,分娩时胎盘大小无差异。对于男性来说,妊娠中期坐着时间过长与胎盘重量(p = 0.001)和胎盘表面积(p = 0.012)降低以及出生体重与胎盘重量(BWPW)比(p = 0.042)升高有关,而胎盘生长因子没有变化。妊娠中期中等体积PA与男性胎盘中较低的VEGFA mRNA表达(p = 0.005)和女性新生儿较高的腹围(p = 0.042)相关,胎盘重量或出生体重在两性中没有总体差异。结论:本研究结果表明,妊娠中期可能是与母体活动有关的胎儿-胎盘生长规划的重要时间点。我们的研究结果强调了怀孕期间减少坐着时间的独立好处,尤其是对怀男性胎儿的女性。
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引用次数: 0
Trophoblastic epithelial-mesenchymal transition with consecutive fibrosis: A cause of reduced placental function in hyperglycemic pregnancies?
IF 3 2区 医学 Q2 DEVELOPMENTAL BIOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.placenta.2024.10.042
Lara Hausdorf , Silke Große , Anne Rüllich , Alexander Berndt , Nikolaus Gaßler , Tanja Groten
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引用次数: 0
Placental transfer of chemicals: Ex vivo placental perfusion model
IF 3 2区 医学 Q2 DEVELOPMENTAL BIOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.placenta.2024.10.047
Line Mathiesen , Lisbeth E. Knudsen
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引用次数: 0
Challenging the Syncytin-1 receptor dualism: Implications for cell fusion in the human placenta
IF 3 2区 医学 Q2 DEVELOPMENTAL BIOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.placenta.2024.10.056
Kateřina Trejbalová , Kryštof Štafl , Martin Trávníček , Anna Janovská , Jiří Hejnar
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引用次数: 0
Endometrial gland-derived extracellular vesicles and their miRNA content
IF 3 2区 医学 Q2 DEVELOPMENTAL BIOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.placenta.2024.10.040
Molly Rutt , Alexandra J. Kermack , Ka Ying Bonnie Ng , James W. Hounslow , Sarah F. Newbury , Rohan M. Lewis , Ying C. Cheong , Jane K. Cleal
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引用次数: 0
Microphysiological models of the human placenta to study Brucella infections and antibiotic treatment during pregnancy
IF 3 2区 医学 Q2 DEVELOPMENTAL BIOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.placenta.2024.10.029
Odysseas Chaliotis , Julia A. Boos , Maren Ketterer , Christoph Dehio , Andreas Hierlemann
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引用次数: 0
Regulation of macrophage polarization by metformin through inhibition of TLR4/NF-κB pathway to improve pre-eclampsia 二甲双胍通过抑制TLR4/NF-κB通路调节巨噬细胞极化改善先兆子痫
IF 3 2区 医学 Q2 DEVELOPMENTAL BIOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.placenta.2025.01.002
Wei Shen , Qingfu Wang , Guofang Shen , Meiling Gu , Qifeng Shen , Ailan Zhang , Xiaohong Zhu

Introduction

Pre-eclampsia (PE) is a pregnancy complication featuring hypertension and proteinuria. Metformin exerts clinically preventive effects on PE with an unspecified mechanism.

Methods

Placental tissues from PE patients and normal pregnant (NP) women were collected. Twenty-four pregnant mice were divided into control, PE (40 μg/kg lipopolysaccharides (LPS)-induced modeling), aspirin, and metformin groups. After acquisition of bone marrow-derived macrophages (BMDM) and THP-1 cells, cells were categorized into control, LPS (100 ng/mL), metformin, and metformin + toll-like receptor 4 (TLR4) agonist RS 09 groups. Inflammatory factors and macrophage polarization were detected by ELISA, flow cytometry, immunofluorescence, immunohistochemistry, and qRT-PCR methods. TLR4/Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway protein expression was examined using Western blot.

Results

Both PE patients and PE-like mice enhanced inducible nitric oxide synthase (iNOS), TLR4, p-NF-κB/NF-κB, and p-inhibitor of NF-κB (IκBα)/IκBα expression, and lower arginase 1 (Arg-1) expression. Moreover, metformin treatment in PE-like mice increased fetal number and weight and reduced hypertension, proteinuria, insulin resistance, tumor necrosis factor-α (TNF-α), IL-6, IL-1β, chemokine ligand 4 (CCL4), C-X-C motif chemokine ligand 2 (CXCL2) expression and M1 macrophage polarization, with similar inhibition to aspirin. In LPS-induced cells, metformin had the same effects mentioned above. Decreased TLR4, p-NF-κB/NF-κB, and p-IκBα/IκBα protein expression was caused by metformin both in vivo and in vitro. In vitro, RS 09 intervention inhibited anti-inflammatory and pro-M2 polarizing effects of metformin, activating TLR4/NF-κB pathway.

Conclusion

Metformin may ameliorate PE by promoting M2 macrophage polarization through up-regulating TLR4/NF-κB pathway, laying theoretical basis for metformin clinical application in PE.
子痫前期(PE)是一种以高血压和蛋白尿为特征的妊娠并发症。二甲双胍对PE具有临床预防作用,其机制尚未明确。方法:收集PE患者和正常孕妇的胎盘组织。将24只孕鼠分为对照组、PE (40 μg/kg脂多糖诱导造模)组、阿司匹林组和二甲双胍组。获取骨髓源性巨噬细胞(BMDM)和THP-1细胞后,将细胞分为对照组、LPS (100 ng/mL)组、二甲双胍组和二甲双胍+ toll样受体4 (TLR4)激动剂rs09组。采用ELISA、流式细胞术、免疫荧光、免疫组织化学、qRT-PCR等方法检测炎症因子和巨噬细胞极化。Western blot检测活化B细胞TLR4/核因子κ轻链增强子(NF-κB)通路蛋白表达。结果:PE患者和PE样小鼠诱导型一氧化氮合酶(iNOS)、TLR4、p-NF-κB/NF-κB、NF-κB抑制因子(i -κB α)/ i -κB α表达增强,精氨酸酶1 (Arg-1)表达降低。此外,二甲双胍治疗pe样小鼠可增加胎数和体重,降低高血压、蛋白尿、胰岛素抵抗、肿瘤坏死因子-α (TNF-α)、IL-6、IL-1β、趋化因子配体4 (CCL4)、C-X-C基元趋化因子配体2 (CXCL2)表达和M1巨噬细胞极化,其抑制作用与阿司匹林相似。在lps诱导的细胞中,二甲双胍具有上述相同的作用。体内外二甲双胍均可降低TLR4、p-NF-κB/NF-κB、p -κB α/ i -κB α蛋白的表达。在体外,rs09干预抑制二甲双胍的抗炎和促m2极化作用,激活TLR4/NF-κB通路。结论:二甲双胍可能通过上调TLR4/NF-κB通路促进M2巨噬细胞极化,从而改善PE,为二甲双胍在PE中的临床应用奠定理论基础。
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引用次数: 0
Platelet-derived factors modulate gene expression profile of human trophoblasts
IF 3 2区 医学 Q2 DEVELOPMENTAL BIOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.placenta.2024.10.050
Freya Lyssy , Désirée Forstner , Jacqueline Guettler , Nadja Kupper , Kaja Ujčič , Stefan Wernitznig , Lena Neuper , Christine Daxboeck , Amin El-Heliebi , Julian C. Krappinger , Julia Feichtinger , Gerhard Cvirn , Anna-Lena Hoebler , Juergen Pollheimer , Joanna L. James , Martin Gauster
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引用次数: 0
期刊
Placenta
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