Placenta最新文献_第2页

Neuroplacental Interactions in early human development: Insights from selective acute neuronal necrosis 早期人类发育中的神经胎盘相互作用：来自选择性急性神经元坏死的见解。

IF 2.5 2区医学 Q2 DEVELOPMENTAL BIOLOGY

Placenta

Pub Date : 2026-01-17 DOI: 10.1016/j.placenta.2026.01.012

Sara Quinones , María Isabel Esteban-Rodríguez , Clara Simon de Blas , Marta De Uribe-Viloria , Víctor Macarrón , Eva Paola Sánchez-López , Gabriela Barrios , Abraham Andreu-Cervera , Verónica Company , Miguel Martínez-Sempere , Eva Maranillo , Isabel Adrados , Rita María Regojo , Eduardo Puelles

Introduction

The correct development of the central nervous system depends largely on the last two trimesters of gestation and the early neonatal period. Neurological lesions are common in autopsies, being one of the most relevant, selective acute neuronal necrosis, a manifestation of hypoxic-ischemic encephalopathy. This study aimed to analyse the distribution of selective acute neuronal necrosis (SANN) and its association with placental lesions, clinical factors and other central nervous system (CNS) abnormalities.

Methods

From 1090 autopsies performed, 205 cases (18.8 %) with SANN were identified. Placental diagnoses followed the Amsterdam Consensus. Statistical analysis included logistic regression and non-parametric tests.

Results

Placental examination was available in 122 of the 205 SANN cases. The most frequent placental patterns were maternal vascular malperfusion in 55.7 %, fetal vascular malperfusion in 38.5 %, chronic villitis in 31.1 %, and ascending intrauterine infection in 24.6 %. The presence of placental lesions was significantly associated with increased risk of cerebral neocortex and pons involvement.

Lower gestational age (GA) was associated with basal ganglia and cerebellar cortex involvement, whereas higher GA was linked to cerebral neocortex involvement. Live-born individuals presented more hippocampal and midbrain involvement. Males showed more hippocampal involvement, and females more cerebellar cortex involvement.

Other CNS abnormalities were found in 71.3 % of SANN cases, mainly gray matter gliosis (60 %), white matter gliosis (43.4 %), haemorrhages (30.2 %), and neuronal migration disorders (8.8 %).

Discussion

These findings highlight the close relationship between placental lesions and SANN, supporting the importance of CNS and placental assessment in these autopsies.

中枢神经系统的正确发育在很大程度上取决于妊娠的最后两个月和新生儿早期。神经病变在尸检中很常见，是最相关的，选择性急性神经元坏死，缺氧缺血性脑病的一种表现。本研究旨在分析选择性急性神经元坏死（SANN）的分布及其与胎盘病变、临床因素和其他中枢神经系统（CNS）异常的关系。方法：在1090例尸检中，鉴定出205例（18.8%）伴有SANN。胎盘诊断遵循阿姆斯特丹共识。统计分析包括逻辑回归和非参数检验。结果：205例SANN中有122例进行了胎盘检查。最常见的胎盘类型为母体血管灌注不良（55.7%）、胎儿血管灌注不良（38.5%）、慢性绒毛炎（31.1%）和上升宫内感染（24.6%）。胎盘病变的存在与大脑新皮层和脑桥受累的风险增加显著相关。低胎龄与基底神经节和小脑皮层受累有关，而高胎龄与大脑新皮层受累有关。活产儿的海马和中脑参与程度更高。男性表现出更多的海马参与，而女性表现出更多的小脑皮层参与。在71.3%的SANN病例中发现其他中枢神经系统异常，主要是灰质胶质瘤（60%）、白质胶质瘤（43.4%）、出血（30.2%）和神经元迁移障碍（8.8%）。讨论：这些发现强调了胎盘病变与SANN之间的密切关系，支持了CNS和胎盘评估在这些尸检中的重要性。

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引用次数: 0

Structural alterations in the placental villous tree in well-controlled gestational diabetes mellitus 控制良好的妊娠糖尿病患者胎盘绒毛树的结构改变

IF 2.5 2区医学 Q2 DEVELOPMENTAL BIOLOGY

Placenta

Pub Date : 2026-01-16 DOI: 10.1016/j.placenta.2026.01.010

N. Barapatre , L. Halm , C. Schmitz , F.E. von Koch , C. Kampfer , H-G. Frank

Introduction

A poorly controlled gestational diabetes mellitus (GDM), a metabolic disorder affecting glucose regulation, can lead to macrosomia in both, the placenta and the fetus. A well-managed GDM usually results in an uncomplicated pregnancy. Though some qualitative histopathological changes have been described in such uncomplicated pregnancies, a quantitative description of the structural alterations is still missing. The aim of this study is to assess the villous trophoblast and the villous tree quantitatively in GDM placentas, stratified according to the fetal sex.

Methods

The villous trees from 20 placentas (10 female and 10 male) affected by GDM and 20 Control placentas (10 female and 10 male) were investigated quantitatively by Stereology and 3D microscopy. The measurement of partial volumes of contractile and non-contractile parts of the villous tree was based on immunohistochemical detection of perivascular myofibroblasts. The villous trophoblast was assessed by 3D microscopy to measure the nuclear surface density.

Results

Only the female GDM placentas show an increase in the density of proliferative trophoblast nuclei and a decrease in the density of non-proliferative trophoblast nuclei. The branching index is reduced in GDM placentas irrespective of the sex. No significant difference was observed in the volumes of the villous tree, the intervillous space, and the fetal vessels. Similarly, the diffusion distance remained unchanged.

Conclusion

Even in well-controlled GDM pregnancies, the villous trophoblast shows a sexually dimorphic alteration in the density of proliferative and non-proliferative nuclei. The branching index, however, is reduced for both villous compartments, independent of fetal sex.

妊娠期糖尿病（GDM）是一种影响血糖调节的代谢紊乱，控制不良可导致胎盘和胎儿的巨大儿。管理良好的GDM通常会导致无并发症的妊娠。虽然一些定性的组织病理学变化已被描述在这种无并发症的妊娠，定量描述的结构改变仍然缺失。本研究的目的是定量评估GDM胎盘的绒毛滋养细胞和绒毛树，并根据胎儿性别进行分层。方法对20例GDM患者胎盘（雌雄各10例）和对照组胎盘（雌雄各10例）的绒毛树进行立体观察和三维显微镜观察。绒毛树可收缩部分和非收缩部分的部分体积测量是基于血管周围肌成纤维细胞的免疫组化检测。利用三维显微镜测量绒毛滋养细胞的核表面密度。结果只有GDM母胎盘增生性滋养细胞核密度增加，非增生性滋养细胞核密度降低。不论性别，GDM胎盘的分支指数都降低。在绒毛树、绒毛间隙和胎血管的体积上没有观察到显著差异。同样，扩散距离保持不变。结论即使在控制良好的妊娠期，绒毛滋养细胞在增殖核和非增殖核的密度上也表现出性别二态改变。然而，分枝指数在两个长绒毛室中都降低了，与胎儿性别无关。

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引用次数: 0

Exploring placental ultrastructure: A review of electron microscopy techniques and emerging methods for resolving 3D organelle architecture. 探索胎盘超微结构：电子显微镜技术和新兴方法的综述，以解决三维细胞器结构。

IF 2.5 2区医学 Q2 DEVELOPMENTAL BIOLOGY

Placenta

Pub Date : 2026-01-16 DOI: 10.1016/j.placenta.2026.01.009

Siddharth Acharya, Eric Hanssen, James C Bouwer, John E Schjenken, Kirsty G Pringle, Roger Smith, Joshua J Fisher

Trophoblast cells line the surface of placental villi, facilitating the exchange of nutrients, gases, and wastes between the maternal and fetal circulations. The fusion of cytotrophoblast (CTB) cells into the surrounding multinucleated syncytiotrophoblast (STB), is accompanied by a shift in cellular ultrastructure (subcellular architecture). Mitochondria undergo a remarkable decrease in size and alteration in morphology following trophoblast differentiation, and have thus been the subject of investigations due to their crucial role in producing energy for placental development. Observing this shift in structure has relied on the use of electron microscopy, which has offered insights into underlying mitochondrial functions. Since the initial use of electron microscopy to study villous trophoblasts in the 1950s, novel techniques have emerged that have the capacity to interrogate placental ultrastructure with unprecedented resolution. This review discusses the evolution of electron microscopy techniques to study the placenta over the last 70 years. Moreover, we discuss emerging methods for resolving 3D organelle structure within the placenta, which offer more physiologically pertinent information and context for complex topologies. Further, we discuss advanced methods of cryo-electron tomography (cryo-ET) that present the placental field with an exciting opportunity to determine the complex relationship between mitochondrial architecture and protein structure in the human placenta. By specifically focusing on mitochondrial imaging, we showcase the capacity for volume electron microscopy and cryo-ET to reveal the role of organelle structure in placental development.

滋养细胞排列在胎盘绒毛表面，促进母体和胎儿循环之间的营养物质、气体和废物的交换。细胞滋养层细胞（CTB）与周围的多核合胞滋养层细胞（STB）融合，伴随着细胞超微结构（亚细胞结构）的改变。在滋养层分化后，线粒体的大小显著减小，形态发生显著改变，由于其在胎盘发育中产生能量的关键作用，线粒体一直是研究的主题。观察这种结构上的变化依赖于电子显微镜的使用，它提供了对线粒体潜在功能的见解。自20世纪50年代首次使用电子显微镜研究绒毛滋养层细胞以来，新技术已经出现，能够以前所未有的分辨率询问胎盘超微结构。本文综述了近70年来电子显微镜技术在胎盘研究中的发展。此外，我们讨论了解决胎盘内三维细胞器结构的新兴方法，这为复杂的拓扑结构提供了更多的生理学相关信息和背景。此外，我们还讨论了冷冻电子断层扫描（cryo-ET）的先进方法，该方法为胎盘领域提供了一个令人兴奋的机会，可以确定人类胎盘中线粒体结构和蛋白质结构之间的复杂关系。通过特别关注线粒体成像，我们展示了体积电子显微镜和冷冻et的能力，以揭示细胞器结构在胎盘发育中的作用。

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引用次数: 0

Aberrant neural crest cells migration leads to melanocyte presence in the umbilical cord 异常神经嵴细胞迁移导致黑素细胞存在于脐带

IF 2.5 2区医学 Q2 DEVELOPMENTAL BIOLOGY

Placenta

Pub Date : 2026-01-14 DOI: 10.1016/j.placenta.2026.01.008

Louis Samson , Stephanie Worrell , Cláudia M. Salgado , Emilio Medina-Ceballos , Daisy Wu , Lauren B. Skvarca , Natalie I. Larsen , Nicole N. Balmer , Ona Marie Faye-Petersen , Robert Bendon , Stewart Cramer , Miguel Reyes-Múgica

Background

Systematic evaluation of the umbilical cord is an integral part of placental examination. Among the important parameters of this exam is the assessment of visible lesions such as knots and discoloration. The latter can be due to funisitis (yellow-white), meconium staining (green), vascular congestion (red-blue), or maternal hyperbilirubinemia (yellow). This case series presents fifteen examples of umbilical cord lesions characterized by foci of brown-black discoloration caused by melanin deposition.

Methods

Placental pathology reports from our institutions mentioning melanocytes or melanin in the umbilical cord were reviewed, and the slides pulled for histologic analysis by members of the pathology team. Immunohistochemical (SOX10, Melan-A, PHOX2B, and CD56) and histochemical (Fontana-Masson) staining was performed retrospectively on the umbilical cord sections.

Results

Fifteen cases of umbilical cord with grossly visible brown linear stippling or punctate discoloration were confirmed. Microscopic examination showed scattered SOX10-positive melanocytes in the amnion layer with melanin deposition and uptake by the amniocytes. Nine of the fifteen infants and none of the mothers had congenital melanocytic nevi.

Conclusion

To the best of our knowledge, this is the first description of melanocytes and melanin pigment in the umbilical cord. We propose that an aberrant migration of neural crest cells into the umbilical cord, with subsequent differentiation into melanocytes, is the most likely pathogenesis.

背景：脐带的系统评估是胎盘检查的一个组成部分。该检查的重要参数之一是评估可见病变，如结和变色。后者可由尿道炎（黄白色）、胎粪染色（绿色）、血管充血（红蓝色）或母体高胆红素血症（黄色）引起。本病例系列介绍了15例脐带病变的特点是由黑色素沉积引起的棕黑色变色灶。方法回顾我院有关黑素细胞或脐带黑色素的胎盘病理报告，病理小组成员将切片进行组织学分析。对脐带切片进行回顾性免疫组化（SOX10、Melan-A、PHOX2B和CD56）和组织化学（Fontana-Masson）染色。结果15例脐带有明显可见的褐色线状斑点或点状变色。镜下可见羊膜内散在的sox10阳性黑色素细胞，并有黑色素沉积和被羊膜细胞摄取。15名婴儿中有9名患有先天性黑素细胞痣，没有母亲患有先天性黑素细胞痣。结论据我们所知，这是对脐带黑色素细胞和黑色素色素的首次描述。我们提出，神经嵴细胞异常迁移到脐带，随后分化为黑素细胞，是最可能的发病机制。

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引用次数: 0

Corrigendum to “-mediated DNA hydroxymethylation of TGFB1 is related to selective intrauterine growth restriction in monochorionic twin pregnancies” [Placenta (144), December 2023, Pages 45–54] “介导的TGFB1 DNA羟甲基化与单绒毛膜双胎妊娠选择性宫内生长限制有关”的更正[胎盘（144），2023年12月，45-54页]

IF 2.5 2区医学 Q2 DEVELOPMENTAL BIOLOGY

Placenta

Pub Date : 2026-01-13 DOI: 10.1016/j.placenta.2026.01.007

Jiayi Jiang , Dianjie Li , Yixiang Zhong, Yi Zhang, Mei Zhong

引用次数: 0

Immunohistochemical analysis of placental Netrin-1, Netrin-4, and UNC5B in preeclampsia 子痫前期胎盘Netrin-1、Netrin-4和UNC5B的免疫组化分析。

IF 2.5 2区医学 Q2 DEVELOPMENTAL BIOLOGY

Placenta

Pub Date : 2026-01-10 DOI: 10.1016/j.placenta.2026.01.006

Deniz Aydın Ceylan , Cihan Kabukçu , Yeliz Arman Karakaya

Introduction

Preeclampsia (PE) is a hypertensive disorder of pregnancy characterized by impaired placental angiogenesis and an imbalance between pro- and anti-angiogenic factors. Netrin-1, Netrin-4, and their receptor UNC5B are critical modulators of vascular development. This study investigated their immunohistochemical expression in preeclamptic and healthy placentas.

Methods

Placental tissues from 96 women with PE and 71 healthy term controls were analyzed. Immunohistochemistry was performed on tissue microarrays, and immunoreactivity scores (IRS) were calculated based on staining intensity and extent. Expression profiles were compared between groups and across disease severity and gestational age subgroups.

Results

Netrin-1 expression was significantly reduced in preeclamptic placentas compared with controls (mean IRS 3.46 ± 2.57 vs. 6.77 ± 3.17; p < 0.0001), whereas Netrin-4 and UNC5B were markedly upregulated (Netrin-4: 8.60 ± 3.22 vs. 1.92 ± 1.59; UNC5B: 4.75 ± 1.95 vs. 3.49 ± 1.30; all p < 0.0001). Netrin-1 remained consistently decreased across severity subgroups, while Netrin-4 expression was significantly higher in severe versus non-severe PE (p = 0.002). Expression levels did not differ between early- and late-onset PE. Correlation analysis showed a negative association between Netrin-1 and Netrin-4 (r = −0.425) and a positive correlation between Netrin-4 and UNC5B (r = 0.439) (both p < 0.0001).

Conclusion

PE is associated with a coordinated shift in the placental Netrin signaling axis, characterized by downregulation of the pro-angiogenic Netrin-1 and upregulation of the anti-angiogenic ligand Netrin-4 and receptor UNC5B. These findings suggest that Netrin-mediated angiogenic imbalance may play a key role in the pathogenesis of preeclampsia.

子痫前期（PE）是一种以胎盘血管生成受损和促血管生成因子与抗血管生成因子失衡为特征的妊娠高血压疾病。Netrin-1、Netrin-4及其受体UNC5B是血管发育的关键调节剂。本研究探讨了它们在子痫前期和健康胎盘中的免疫组化表达。方法：对96例PE孕妇和71例健康足月对照组的胎盘组织进行分析。对组织微阵列进行免疫组化，并根据染色强度和程度计算免疫反应性评分（IRS）。表达谱在组间、疾病严重程度和胎龄亚组间进行比较。结果：与对照组相比，子痫前期胎盘中Netrin-1的表达显著降低（平均IRS为3.46±2.57比6.77±3.17）；p结论：PE与胎盘Netrin信号轴的协同移位有关，其特征是促血管生成的Netrin-1下调，而抗血管生成配体Netrin-4和受体UNC5B上调。这些发现提示，netrin介导的血管生成失衡可能在子痫前期的发病机制中起关键作用。

{"title":"Immunohistochemical analysis of placental Netrin-1, Netrin-4, and UNC5B in preeclampsia","authors":"Deniz Aydın Ceylan , Cihan Kabukçu , Yeliz Arman Karakaya","doi":"10.1016/j.placenta.2026.01.006","DOIUrl":"10.1016/j.placenta.2026.01.006","url":null,"abstract":"<div><h3>Introduction</h3><div>Preeclampsia (PE) is a hypertensive disorder of pregnancy characterized by impaired placental angiogenesis and an imbalance between pro- and anti-angiogenic factors. Netrin-1, Netrin-4, and their receptor UNC5B are critical modulators of vascular development. This study investigated their immunohistochemical expression in preeclamptic and healthy placentas.</div></div><div><h3>Methods</h3><div>Placental tissues from 96 women with PE and 71 healthy term controls were analyzed. Immunohistochemistry was performed on tissue microarrays, and immunoreactivity scores (IRS) were calculated based on staining intensity and extent. Expression profiles were compared between groups and across disease severity and gestational age subgroups.</div></div><div><h3>Results</h3><div>Netrin-1 expression was significantly reduced in preeclamptic placentas compared with controls (mean IRS 3.46 ± 2.57 vs. 6.77 ± 3.17; <em>p</em> < 0.0001), whereas Netrin-4 and UNC5B were markedly upregulated (Netrin-4: 8.60 ± 3.22 vs. 1.92 ± 1.59; UNC5B: 4.75 ± 1.95 vs. 3.49 ± 1.30; all <em>p</em> < 0.0001). Netrin-1 remained consistently decreased across severity subgroups, while Netrin-4 expression was significantly higher in severe versus non-severe PE (<em>p</em> = 0.002). Expression levels did not differ between early- and late-onset PE. Correlation analysis showed a negative association between Netrin-1 and Netrin-4 (<em>r</em> = −0.425) and a positive correlation between Netrin-4 and UNC5B (<em>r</em> = 0.439) (both <em>p</em> < 0.0001).</div></div><div><h3>Conclusion</h3><div>PE is associated with a coordinated shift in the placental Netrin signaling axis, characterized by downregulation of the pro-angiogenic Netrin-1 and upregulation of the anti-angiogenic ligand Netrin-4 and receptor UNC5B. These findings suggest that Netrin-mediated angiogenic imbalance may play a key role in the pathogenesis of preeclampsia.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"175 ","pages":"Pages 7-15"},"PeriodicalIF":2.5,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146011635","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}

引用次数: 0

Adeno-associated viral vector-mediated gene delivery and shRNA knockdown in primary human cytotrophoblasts 人原代细胞滋养层细胞中腺相关病毒载体介导的基因传递和shRNA敲除

IF 2.5 2区医学 Q2 DEVELOPMENTAL BIOLOGY

Placenta

Pub Date : 2026-01-10 DOI: 10.1016/j.placenta.2026.01.005

Hiromichi Yamamoto , Masato Tamari , Seiji Wada , Hironori Takahashi , Hiromi Yoshida-Komiya , Hirohisa Saito , Hideaki Morita , Kenji Matsumoto , Kenichiro Motomura

The placenta is essential for fetal growth and the maintenance of pregnancy. Primary human cytotrophoblasts (CTBs) provide a physiologically relevant model of this transient organ, yet their use has been limited by the difficulty of genetic manipulation. Recombinant adeno-associated virus (AAV) vectors, widely used to modulate gene expression in other systems, offer low immunogenicity, low cytotoxicity, and high efficiency in primary cells. Here, we provide proof of concept of an AAV-mediated gene delivery approach for primary CTBs. This platform enables in-depth, cell-biological studies to elucidate molecular mechanisms of human placental biology and pathology.

胎盘对胎儿生长和维持妊娠至关重要。原代人细胞滋养细胞（CTBs）提供了这一短暂器官的生理相关模型，但其应用受到遗传操作难度的限制。重组腺相关病毒（AAV）载体在原代细胞中具有低免疫原性、低细胞毒性和高效率，广泛用于调节其他系统中的基因表达。在这里，我们提供了aav介导的原发性CTBs基因传递方法的概念证明。该平台使深入的细胞生物学研究能够阐明人类胎盘生物学和病理学的分子机制。

引用次数: 0

Maternal soluble suppression of Tumorigenicity-2 as a biomarker for fetal growth restriction: Clinical correlations and diagnostic performance 母体可溶性抑制致瘤性-2作为胎儿生长受限的生物标志物：临床相关性和诊断性能

IF 2.5 2区医学 Q2 DEVELOPMENTAL BIOLOGY

Placenta

Pub Date : 2026-01-09 DOI: 10.1016/j.placenta.2026.01.004

Sadun Sucu , Sadullah Özkan , Alperen Aksan , Dilara Kurt , Belgin Savran Üçok , Turhan Çağlar

Introduction

To investigate maternal serum levels of soluble suppression of tumorigenicity-2 (sST2) in pregnancies complicated by fetal growth restriction (FGR), and to evaluate its diagnostic utility and association with adverse neonatal outcomes.

Methods

This prospective observational study comprised 88 singleton pregnancies, including 44 FGR cases and 44 healthy controls matched for gestational age. FGR was classified as early or late onset using Delphi consensus criteria. Maternal serum sST2 levels were measured between 28 and 37 weeks of gestation by ELISA. Correlation analyzes and ROC curve analyzes were performed to evaluate diagnostic performance and associations with clinical parameters.

Results

sST2 levels were significantly higher in the FGR group compared to controls (p = 0.008). In the control group, sST2 levels showed a strong positive correlation with gestational age (r = 0.631, p < 0.001), no such correlation was observed in FGR pregnancies (r = 0.098, p = 0.529). ROC analysis demonstrated moderate diagnostic accuracy of sST2 for FGR (AUC = 0.665, p = 0.004), with high sensitivity (98 %) at a low cut-off (>0.28 ng/ml) and a specificity that reached 90 % at higher thresholds. sST2 also predicted adverse composite neonatal outcomes in FGR cases with an AUC of 0.689.

Discussion

Maternal serum sST2 levels are significantly elevated in FGR pregnancies and may serve as a biomarker for placental dysfunction. Although the sST2 level is not specific enough as a stand-alone diagnostic tool, it can help in risk stratification when used in conjunction with other clinical or biochemical markers.

研究妊娠合并胎儿生长受限（FGR）孕妇血清可溶性抑制致瘤性-2 （sST2）水平，并评估其诊断价值及其与新生儿不良结局的关系。方法本前瞻性观察研究纳入88例单胎妊娠，包括44例FGR病例和44例胎龄匹配的健康对照。使用德尔菲共识标准将FGR分为早发或晚发。采用ELISA法测定妊娠28 ~ 37周孕妇血清sST2水平。进行相关分析和ROC曲线分析，评价诊断效能及其与临床参数的相关性。结果FGR组ssst2水平显著高于对照组（p = 0.008）。在对照组中，sST2水平与胎龄呈正相关（r = 0.631, p < 0.001），在FGR妊娠组中，sST2水平与胎龄无相关性（r = 0.098, p = 0.529）。ROC分析显示，sST2对FGR的诊断准确度中等（AUC = 0.665, p = 0.004），在低临界值（>0.28 ng/ml）下具有高灵敏度（98%），在较高阈值下特异性达到90%。sST2还预测FGR病例的不良综合新生儿结局，AUC为0.689。FGR孕妇血清sST2水平显著升高，可作为胎盘功能障碍的生物标志物。虽然sST2水平作为一种单独的诊断工具不够特异性，但当与其他临床或生化指标结合使用时，它可以帮助进行风险分层。

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引用次数: 0

Placental gene expression signatures based on maternal parity 基于母体胎次的胎盘基因表达特征

IF 2.5 2区医学 Q2 DEVELOPMENTAL BIOLOGY

Placenta

Pub Date : 2026-01-06 DOI: 10.1016/j.placenta.2026.01.002

Lylach Haizler-Cohen , Guisong Wang , Tesfa Dejenie Habtewold , Prabhavi Wijesiriwardhana , Katherine L. Grantz , Fasil Tekola-Ayele

Introduction

Nulliparity is associated with adverse pregnancy outcomes including preeclampsia, preterm birth, lower birth weight and stillbirth although mechanisms are unclear. Placental gene expression differences, which also vary by fetal sex, may drive altered placental function and explain pregnancy outcome differences between nulliparous and multiparous women. This study aims to identify placental gene expression differences based on parity and examine their relationship with birth weight.

Methods

RNA sequencing was performed on placental samples collected at delivery as part of the NICHD Fetal Growth Studies. Differentially expressed genes between placentas of nulliparous (n = 34) and multiparous (n = 41) participants were determined in the full cohort and stratified by fetal sex. Weighted gene co-expression network analysis was performed to identify co-expression modules associated with parity. Correlation of differentially expressed genes and co-expression modules with birth weight was assessed.

Results

Five differentially expressed genes were identified (FDR p < 0.05) including DDX5 (higher expression in multiparas in full cohort), ANKRD33 and SLITRK6 (higher in multiparas in female sub-cohort), and IL1B and MTCO1P40 (higher in nulliparas in female sub-cohort). Two gene co-expression modules, “Grey60” and “Tan”, were negatively associated with multiparity. The DDX5 and ILB1 genes, and the “Grey60” module were significantly correlated with birth weight within the parity group that exhibited lower expression. Genes in the two co-expression modules were enriched for pathways related to immune response, cardiovascular and reproductive system development, and cancer.

Discussion

Placental gene expression differences between nulliparas and multiparas may in part underlie neonatal outcomes that differ by parity and fetal sex.

无产与不良妊娠结局相关，包括先兆子痫、早产、低出生体重和死胎，但机制尚不清楚。胎盘基因表达的差异，也因胎儿性别而异，可能导致胎盘功能的改变，并解释了无产和多产妇女妊娠结局的差异。本研究旨在确定基于胎次的胎盘基因表达差异，并研究其与出生体重的关系。方法对分娩时收集的胎盘样本进行srna测序，作为NICHD胎儿生长研究的一部分。在全队列中，对未产（n = 34）和多产（n = 41）受试者的胎盘差异表达基因进行了测定，并按胎儿性别分层。进行加权基因共表达网络分析，以确定与胎次相关的共表达模块。评估差异表达基因和共表达模块与出生体重的相关性。结果共鉴定出5个差异表达基因（FDR p < 0.05），包括DDX5（在完整队列中多paras中表达较高）、ANKRD33和SLITRK6（在女性亚队列中多paras中表达较高）、IL1B和MTCO1P40（在女性亚队列中无paras中表达较高）。两个基因共表达模块“Grey60”和“Tan”与多胎呈负相关。在低表达胎次组中，DDX5和ILB1基因以及“Grey60”模块与出生体重显著相关。两个共表达模块中的基因丰富，与免疫反应、心血管和生殖系统发育以及癌症相关。无胎和多胎胎盘基因表达的差异可能在一定程度上导致胎次和胎儿性别不同的新生儿结局。

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引用次数: 0

Maternal hypothyroidism and diabetes alter plasma concentration and placental signaling of sex steroids in rats 母亲甲状腺功能减退和糖尿病改变大鼠性类固醇的血浆浓度和胎盘信号

IF 2.5 2区医学 Q2 DEVELOPMENTAL BIOLOGY

Placenta

Pub Date : 2026-01-06 DOI: 10.1016/j.placenta.2026.01.003

Jeane Martinha dos Anjos Cordeiro, Bianca Reis Santos, Adriana Lopes da Silva, Luciano Cardoso Santos, Juneo Freitas Silva

Introduction

Proper hormonal signaling at the maternal-fetal interface and adequate placental steroidogenesis are crucial for a successful pregnancy. However, the effects of maternal diabetes (MD) and hypothyroidism (MH) on placental steroidogenic pathways remain poorly characterized. This study investigated the expression of sex hormone receptors and key steroidogenic enzymes at the maternal-fetal interface in rat models of MH and MD.

Methods

At GD18, in both MH (6-propyl-2-thiouracil–induced) and MD (streptozotocin-induced) conditions, maternal hormonal dosage (free T4 or insulin, and E2, P4, and testosterone) were performed, along with placental RT-qPCR and/or immunohistochemistry analyses for steroidogenic pathway markers (ERα/Esr1, PR/Pgr, AR/Ar, Star, Cyp11a1, Hsd17b3, and Hsd3b1).

Results

Both MD and MH dams exhibited reduced fetal weight. These outcomes were associated with elevated plasma estradiol levels in MD rats and reduced testosterone levels in MH rats, while progesterone concentrations remained unchanged in both groups. Both MD and MH resulted in upregulated placental Esr1 expression, whereas MH additionally increased ERα protein levels in the metrial triangle. Regarding the progesterone receptor (PR), MH markedly increased its immunostaining throughout the maternal–fetal interface and both conditions elevated placental Pgr transcript levels. MH also upregulated androgen receptor (AR) protein expression in the decidua and increased placental expression of the steroidogenic enzyme Hsd3b1, while MD elevated placental Ar gene expression.

Conclusion

These findings demonstrate that both MD and, more profoundly, MH disrupt sex steroid homeostasis and receptor expression at the rat maternal–fetal interface.

在母胎界面适当的激素信号和充足的胎盘类固醇生成是成功妊娠的关键。然而，母体糖尿病（MD）和甲状腺功能减退症（MH）对胎盘类固醇生成途径的影响仍不清楚。方法采用GD18，在MH（6-丙基-2-硫脲嘧啶诱导）和MD（链脲素诱导）两种情况下，测定母体激素剂量（游离T4或胰岛素、E2、P4和睾酮），并进行胎盘RT-qPCR和/或免疫组化分析，检测孕激素途径标志物(ERα/Esr1、PR/Pgr、AR/ AR、Star、Cyp11a1、Hsd17b3、和Hsd3b1)。结果MD和MH母鼠均表现出胎儿体重减轻的特点。这些结果与MD大鼠血浆雌二醇水平升高和MH大鼠血浆睾酮水平降低有关，而两组的孕酮浓度保持不变。MD和MH均导致胎盘Esr1表达上调，而MH则增加了子宫三角ERα蛋白水平。在孕激素受体（PR）方面，MH显著增加了其在母胎界面的免疫染色，两种情况下都提高了胎盘中孕激素受体（PR）的转录水平。MH还上调了蜕膜中雄激素受体（AR）蛋白的表达，增加了胎盘中类固醇生成酶Hsd3b1的表达，而MD则升高了胎盘中AR基因的表达。结论这些发现表明，MD和MH更深刻地破坏了大鼠母胎界面的性类固醇稳态和受体表达。

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引用次数: 0