Placenta最新文献_第3页

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。

{"title":"Placental gene expression signatures based on maternal parity","authors":"Lylach Haizler-Cohen , Guisong Wang , Tesfa Dejenie Habtewold , Prabhavi Wijesiriwardhana , Katherine L. Grantz , Fasil Tekola-Ayele","doi":"10.1016/j.placenta.2026.01.002","DOIUrl":"10.1016/j.placenta.2026.01.002","url":null,"abstract":"<div><h3>Introduction</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>Five differentially expressed genes were identified (FDR p < 0.05) including <em>DDX5</em> (higher expression in multiparas in full cohort), <em>ANKRD33</em> and <em>SLITRK6</em> (higher in multiparas in female sub-cohort), and <em>IL1B</em> and <em>MTCO1P40</em> (higher in nulliparas in female sub-cohort). Two gene co-expression modules, “Grey60” and “Tan”, were negatively associated with multiparity. The <em>DDX5</em> and <em>ILB1</em> 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.</div></div><div><h3>Discussion</h3><div>Placental gene expression differences between nulliparas and multiparas may in part underlie neonatal outcomes that differ by parity and fetal sex.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"174 ","pages":"Pages 214-224"},"PeriodicalIF":2.5,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145925047","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

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。

{"title":"Maternal hypothyroidism and diabetes alter plasma concentration and placental signaling of sex steroids in rats","authors":"Jeane Martinha dos Anjos Cordeiro, Bianca Reis Santos, Adriana Lopes da Silva, Luciano Cardoso Santos, Juneo Freitas Silva","doi":"10.1016/j.placenta.2026.01.003","DOIUrl":"10.1016/j.placenta.2026.01.003","url":null,"abstract":"<div><h3>Introduction</h3><div>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.</div></div><div><h3>Methods</h3><div>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/<em>Esr1</em>, PR/<em>Pgr</em>, AR/<em>Ar</em>, <em>Star, Cyp11a1, Hsd17b3</em>, and <em>Hsd3b1</em>).</div></div><div><h3>Results</h3><div>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 <em>Esr1</em> 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 <em>Pgr</em> transcript levels. MH also upregulated androgen receptor (AR) protein expression in the decidua and increased placental expression of the steroidogenic enzyme <em>Hsd3b1</em>, while MD elevated placental <em>Ar</em> gene expression.</div></div><div><h3>Conclusion</h3><div>These findings demonstrate that both MD and, more profoundly, MH disrupt sex steroid homeostasis and receptor expression at the rat maternal–fetal interface.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"174 ","pages":"Pages 235-244"},"PeriodicalIF":2.5,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145925150","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

The receptor activator of nuclear factor κB ligand (RANKL) regulates the biological behavior of trophoblasts through the PI3K/Akt signaling pathway 核因子κB配体受体激活因子（receptor activator of nuclear factor κB ligand， RANKL）通过PI3K/Akt信号通路调控滋养细胞的生物学行为

IF 2.5 2区医学 Q2 DEVELOPMENTAL BIOLOGY

Placenta

Pub Date : 2026-01-05 DOI: 10.1016/j.placenta.2026.01.001

YaLu Fu , QiuYan Zhao , YuChan Wang , WeiJing Yang , XingLong Liu , WeiWei Yang , Xin Tan , YuHan Meng

Introduction

Abnormal function of trophoblasts is a primary cause of recurrent spontaneous abortion (RSA). However, the underlying molecular mechanisms remain unclear, and further explanation is urgently needed. This study aims to explore the effect and potential regulatory mechanisms of RANKL in the biological function of trophoblasts.

Methods

Immunohistochemistry was conducted on villous tissues from RSA patients and people who underwent artificial abortion. Cell proliferation, migration, and invasion were assessed in HTR-8/SVneo and JEG-3 cells using CCK-8, scratch wound healing, and transwell assays. Protein expression was analyzed by western blotting.

Results

The expression of RANKL was significantly lower in villus of RSA patients compared to healthy controls. Recombinant human RANKL (rhRANKL) promoted the proliferation, migration and invasion of trophoblasts, while rhOPG, α-RANKL and MK-2206 (Akt inhibitor) alleviated the effect of rhRANK. Moreover, it may exert the effect through the PI3K/Akt signaling pathway.

Conclusions

Our results demonstrated that downregulation of RANKL in villous tissue was associated with RSA, and that it promoted trophoblasts proliferation, invasion, and migration via the PI3K/Akt pathway. This may help elucidate the molecular pathogenesis of impaired embryo adhesion and implantation capacity.

滋养细胞功能异常是复发性自然流产（RSA）的主要原因。然而，潜在的分子机制尚不清楚，迫切需要进一步的解释。本研究旨在探讨RANKL在滋养细胞生物学功能中的作用及其可能的调控机制。方法对RSA患者和人工流产患者的绒毛组织进行免疫组化。采用CCK-8、划伤愈合和transwell试验评估HTR-8/SVneo和JEG-3细胞的细胞增殖、迁移和侵袭。western blotting分析蛋白表达。结果RSA患者绒毛中RANKL的表达明显低于正常对照组。重组人RANKL （rhRANKL）促进滋养细胞的增殖、迁移和侵袭，而rhOPG、α-RANKL和MK-2206 （Akt抑制剂）则减轻了rhRANK的作用。此外，它可能通过PI3K/Akt信号通路发挥作用。结论绒毛组织中RANKL的下调与RSA相关，并通过PI3K/Akt通路促进滋养细胞增殖、侵袭和迁移。这可能有助于阐明胚胎粘附和着床能力受损的分子发病机制。

{"title":"The receptor activator of nuclear factor κB ligand (RANKL) regulates the biological behavior of trophoblasts through the PI3K/Akt signaling pathway","authors":"YaLu Fu , QiuYan Zhao , YuChan Wang , WeiJing Yang , XingLong Liu , WeiWei Yang , Xin Tan , YuHan Meng","doi":"10.1016/j.placenta.2026.01.001","DOIUrl":"10.1016/j.placenta.2026.01.001","url":null,"abstract":"<div><h3>Introduction</h3><div>Abnormal function of trophoblasts is a primary cause of recurrent spontaneous abortion (RSA). However, the underlying molecular mechanisms remain unclear, and further explanation is urgently needed. This study aims to explore the effect and potential regulatory mechanisms of RANKL in the biological function of trophoblasts.</div></div><div><h3>Methods</h3><div>Immunohistochemistry was conducted on villous tissues from RSA patients and people who underwent artificial abortion. Cell proliferation, migration, and invasion were assessed in HTR-8/SVneo and JEG-3 cells using CCK-8, scratch wound healing, and transwell assays. Protein expression was analyzed by western blotting.</div></div><div><h3>Results</h3><div>The expression of RANKL was significantly lower in villus of RSA patients compared to healthy controls. Recombinant human RANKL (rhRANKL) promoted the proliferation, migration and invasion of trophoblasts, while rhOPG, α-RANKL and MK-2206 (Akt inhibitor) alleviated the effect of rhRANK. Moreover, it may exert the effect through the PI3K/Akt signaling pathway.</div></div><div><h3>Conclusions</h3><div>Our results demonstrated that downregulation of RANKL in villous tissue was associated with RSA, and that it promoted trophoblasts proliferation, invasion, and migration via the PI3K/Akt pathway. This may help elucidate the molecular pathogenesis of impaired embryo adhesion and implantation capacity.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"174 ","pages":"Pages 225-234"},"PeriodicalIF":2.5,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145925051","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

Polystyrene microplastics internalization by term placental chorionic villi explants 足月胎盘绒毛膜绒毛外植体的聚苯乙烯微塑料内化。

IF 2.5 2区医学 Q2 DEVELOPMENTAL BIOLOGY

Placenta

Pub Date : 2026-01-01 DOI: 10.1016/j.placenta.2025.06.002

Aldilane Lays Marques , Rodrigo Weingrill , Stephanie Ospina-Prieto , Keyla Pires , Isadora Cavalcante , Ashelley Kettyllem Sousa , Iasmin Cristina Cavalcante , Lais Oliveira , Samuel Souza , Eduardo Jorge Fonseca , Jacob Garcia , Men-Jean Lee , Johann Urschitz , Alexandre Borbely

Introduction

Microplastics (MPs) are pervasive environmental contaminants increasingly found within human tissues, including the placenta. This study explores the potential of polystyrene (PS)-MPs to cross the placental barrier and their general distribution within term placental chorionic villi explants.

Methods

Term placental chorionic villi explants were exposed up to 72 h to 100 μg/mL of 5 μm-size polystyrene (PS)-MPs, and their internalization was analyzed by optical microscopy, confocal atomic force microscopy (C-AFM) and fluorescence confocal imaging.

Results

The PS-MPs can traverse the placental barrier. Over 72 h of exposure, these particles were not only adsorbed on the surface but also internalized within the syncytiotrophoblast and dispersed through the chorionic villi mesenchyme. Our observations indicate that PS-MPs are found up to 120 μm deep within the villi, suggesting their capability to penetrate deeply into placental tissue. Furthermore, these MPs were surrounded by a thin layer of actin, implying active internalization mechanisms possibly involving macropinocytosis or phagocytosis, although specific pathways in placental tissues remain to be fully elucidated. No evidence of barrier fissures or membrane ruptures was observed, indicating that the internalization process does not disrupt the syncytiotrophoblast barrier integrity.

Discussion

This study underscores the urgent need to understand the implications of such internalization and their effects on placental homeostasis. Given the potential for MPs to influence developmental processes adversely, further research is essential to delineate the mechanisms of MP internalization, possible physiological impacts, and the consequences of fetal exposure.

微塑料（MPs）是普遍存在的环境污染物，越来越多地在人体组织中发现，包括胎盘。本研究探讨了聚苯乙烯(PS)-MPs跨越胎盘屏障的潜力及其在足月胎盘绒毛膜绒毛外植体中的普遍分布。方法：将足月胎盘绒毛膜绒毛外植体暴露于100 μg/mL 5 μm大小的聚苯乙烯(PS)-MPs中72 h，通过光学显微镜、共聚焦原子力显微镜（C-AFM）和荧光共聚焦成像分析其内化情况。结果：PS-MPs能穿过胎盘屏障。暴露72小时后，这些颗粒不仅吸附在表面，而且内化在合体滋养细胞内，并通过绒毛膜绒毛间质分散。我们的观察表明，PS-MPs在绒毛深处可达120 μm，表明它们能够深入胎盘组织。此外，这些MPs被一层薄薄的肌动蛋白包围，这意味着积极的内化机制可能涉及巨噬细胞或吞噬作用，尽管胎盘组织中的具体途径仍有待充分阐明。没有观察到屏障裂缝或膜破裂的证据，表明内化过程不会破坏合体滋养细胞屏障的完整性。讨论：这项研究强调了迫切需要了解这种内化的含义及其对胎盘稳态的影响。考虑到多聚物可能对发育过程产生不利影响，有必要进一步研究多聚物内化的机制、可能的生理影响以及胎儿接触多聚物的后果。

{"title":"Polystyrene microplastics internalization by term placental chorionic villi explants","authors":"Aldilane Lays Marques , Rodrigo Weingrill , Stephanie Ospina-Prieto , Keyla Pires , Isadora Cavalcante , Ashelley Kettyllem Sousa , Iasmin Cristina Cavalcante , Lais Oliveira , Samuel Souza , Eduardo Jorge Fonseca , Jacob Garcia , Men-Jean Lee , Johann Urschitz , Alexandre Borbely","doi":"10.1016/j.placenta.2025.06.002","DOIUrl":"10.1016/j.placenta.2025.06.002","url":null,"abstract":"<div><h3>Introduction</h3><div><span>Microplastics (MPs) are pervasive environmental contaminants increasingly found within human tissues, including the placenta<span><span>. This study explores the potential of polystyrene (PS)-MPs to cross the </span>placental barrier and their general distribution within term placental </span></span>chorionic villi<span> explants.</span></div></div><div><h3>Methods</h3><div><span>Term placental chorionic villi<span> explants<span> were exposed up to 72 h to 100 μg/mL of 5 μm-size polystyrene (PS)-MPs, and their </span></span></span>internalization<span><span> was analyzed by optical microscopy, confocal </span>atomic force microscopy (C-AFM) and fluorescence confocal imaging.</span></div></div><div><h3>Results</h3><div><span><span><span>The PS-MPs can traverse the placental barrier. Over 72 h of exposure, these particles were not only adsorbed on the </span>surface<span> but also internalized within the syncytiotrophoblast<span> and dispersed through the chorionic villi </span></span></span>mesenchyme<span>. Our observations indicate that PS-MPs are found up to 120 μm deep within the villi, suggesting their capability to penetrate deeply into placental tissue. Furthermore, these MPs were surrounded by a thin layer of actin, implying active internalization mechanisms possibly involving </span></span>macropinocytosis<span><span> or phagocytosis, although specific pathways in placental tissues remain to be fully elucidated. No evidence of barrier fissures or </span>membrane ruptures<span> was observed, indicating that the internalization process does not disrupt the syncytiotrophoblast barrier integrity.</span></span></div></div><div><h3>Discussion</h3><div>This study underscores the urgent need to understand the implications of such internalization and their effects on placental homeostasis. Given the potential for MPs to influence developmental processes adversely, further research is essential to delineate the mechanisms of MP internalization, possible physiological impacts, and the consequences of fetal exposure.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"173 ","pages":"Pages 102-110"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144286189","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

Maternal serum heparan sulfate in preeclampsia pathophysiology: Insights from a systematic review and meta-analysis 母体血清硫酸肝素在子痫前期病理生理中的作用：来自系统回顾和荟萃分析的见解。

IF 2.5 2区医学 Q2 DEVELOPMENTAL BIOLOGY

Placenta

Pub Date : 2026-01-01 DOI: 10.1016/j.placenta.2025.04.026

Alejandra María Gómez-Gutiérrez , Angela María Alvarez-Gómez , Juan Carlos Quintana-Castillo , Julio Cesar Bueno-Sánchez , Walter D. Cardona Maya

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.

先兆子痫（PE）是一种高血压疾病，通常发生在怀孕前半期，分娩甚至产后；它与母体器官功能障碍有关，并显著增加母体、胎儿和新生儿的发病率和死亡率。在PE期间，合体滋养细胞和内皮细胞受到损伤，细胞外基质中的分子，如硫酸肝素（HS），可以释放到血液中。因此，本研究旨在通过系统回顾和荟萃分析来评估子痫前期和正常妊娠妇女血清HS水平。为了进行这项系统评价和荟萃分析研究，我们全面检索了PubMed、ScienceDirect和LILACS，并收集了有关HS和先兆子痫的已发表研究。偏倚风险采用纽卡斯尔-渥太华量表评分进行评估。在检索完成后，确定了568项研究，并为本分析检索了4项研究。森林图显示，与非子痫前期妇女相比，子痫前期妇女血清HS升高，标准化平均差异-SMD- 95% CI为1.2(-0.41至2.81)，这种关系在早期PE组中保持不变(SMD 1.05；95% ci(0.22-2.32))。在conclusión中，我们提出HS可能在子痫前期的发病机制中起着至关重要的作用，因为结果显示子痫前期妇女血清中HS分子水平升高。

{"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":"10.1016/j.placenta.2025.04.026","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"173 ","pages":"Pages 63-68"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","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}

引用次数: 0

Review: The potential role of placental extracellular vesicles in blood-brain barrier disruption and neuroinflammation in preeclampsia 综述：胎盘细胞外囊泡在子痫前期血脑屏障破坏和神经炎症中的潜在作用。

IF 2.5 2区医学 Q2 DEVELOPMENTAL BIOLOGY

Placenta

Pub Date : 2026-01-01 DOI: 10.1016/j.placenta.2025.04.001

Carlos Escudero , Manu Vatish

Preeclampsia is a complex pregnancy disorder characterized by hypertension and multisystem organ damage, notably affecting the liver, kidneys, and brain. Eclampsia, a severe form of preeclampsia, is marked by the sudden onset of generalized tonic-clonic seizures. Brain complications, including eclampsia, are responsible for 60–70 % of preeclampsia-related maternal deaths, particularly in low-income regions. Despite the significant impact of brain complications in preeclampsia, their underlying pathophysiology remains unclear. Evidence suggests that brain edema in preeclampsia and eclampsia results from disruption of the blood-brain barrier (BBB). Although direct analysis of the BBB is challenging, in vitro studies indicate that plasma from women with preeclampsia can compromise the BBB, with the specific circulating factors involved still unidentified. Among the potential culprits, recent findings highlight placental-derived small extracellular vesicles (PDsEVs) as key players in BBB disruption observed in preeclampsia. This review examines the role of PDsEVs in the pathophysiology of brain edema associated with preeclampsia, emphasizing areas for future research, including neuroinflammation and neuron dysfunction. Additionally, we discuss the protective role of magnesium sulfate in these processes.

子痫前期是一种以高血压和多系统器官损害为特征的复杂妊娠疾病，主要影响肝、肾和脑。子痫是子痫前期的一种严重形式，其特点是全身性强直阵挛发作的突然发作。脑部并发症，包括子痫，是导致60- 70%子痫前期孕产妇死亡的原因，特别是在低收入地区。尽管脑并发症对子痫前期的影响很大，但其潜在的病理生理机制尚不清楚。有证据表明，子痫前期和子痫的脑水肿是由血脑屏障（BBB）的破坏引起的。尽管直接分析血脑屏障具有挑战性，但体外研究表明，子痫前期妇女的血浆可能损害血脑屏障，具体的循环因子仍未确定。在潜在的罪魁祸首中，最近的研究结果强调胎盘来源的小细胞外囊泡（pdsev）在子痫前期观察到的血脑屏障破坏中起关键作用。本文综述了pdsev在子痫前期脑水肿病理生理中的作用，强调了未来的研究领域，包括神经炎症和神经元功能障碍。并讨论了硫酸镁在这些过程中的保护作用。

{"title":"Review: The potential role of placental extracellular vesicles in blood-brain barrier disruption and neuroinflammation in preeclampsia","authors":"Carlos Escudero , Manu Vatish","doi":"10.1016/j.placenta.2025.04.001","DOIUrl":"10.1016/j.placenta.2025.04.001","url":null,"abstract":"<div><div><span>Preeclampsia<span><span> is a complex pregnancy disorder characterized by hypertension and multisystem organ damage, notably affecting the liver, kidneys, and brain. Eclampsia<span>, a severe form of preeclampsia, is marked by the sudden onset of generalized tonic-clonic seizures. Brain complications, including eclampsia, are responsible for 60–70 % of preeclampsia-related maternal deaths, particularly in low-income regions. Despite the significant impact of brain complications in preeclampsia, their underlying </span></span>pathophysiology<span><span> remains unclear. Evidence suggests that brain edema in </span>preeclampsia and eclampsia results from disruption of the blood-brain barrier (BBB). Although direct analysis of the BBB is challenging, </span></span></span><em>in vitro</em><span> studies indicate that plasma from women with preeclampsia can compromise the BBB, with the specific circulating factors involved still unidentified. Among the potential culprits, recent findings highlight placental-derived small extracellular vesicles (PDsEVs) as key players in BBB disruption observed in preeclampsia. This review examines the role of PDsEVs<span><span> in the pathophysiology<span> of brain edema associated with preeclampsia, emphasizing areas for future research, including </span></span>neuroinflammation<span> and neuron dysfunction. Additionally, we discuss the protective role of magnesium sulfate in these processes.</span></span></span></div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"173 ","pages":"Pages 153-159"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035394","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

Effects of semen inflammation on embryo implantation, placentation, pregnancy outcomes and offspring health 精液炎症对胚胎着床、胎盘、妊娠结局及子代健康的影响。

IF 2.5 2区医学 Q2 DEVELOPMENTAL BIOLOGY

Placenta

Pub Date : 2026-01-01 DOI: 10.1016/j.placenta.2025.02.002

María S. Martinez , Yair A. Chocobar , Yamila Fariz , Daniela A. Paira , Virginia E. Rivero , Rubén D. Motrich

This review explores the critical role of semen inflammation in sperm quality, embryo implantation, placentation, and its broader implications on reproductive health. Chronic inflammation of the male genital tract has been increasingly recognized as a significant factor contributing to infertility. This inflammation not only impairs semen quality but also disrupts the intricate immune cross-talk between the male and female genital tracts, which is essential for successful implantation, placentation and pregnancy. The review synthesizes existing research on the mechanisms by which inflammatory mediators in semen influence the female immune environment, leading to altered uterine receptivity, placental formation, and embryo implantation. Furthermore, the impact of these disruptions on the health and development of the offspring is discussed, highlighting the transgenerational effects of male genital tract inflammation. Through an examination of both animal models and human studies, this review underscores the need for a deeper understanding of the immune interactions in reproductive biology and the potential for novel therapeutic interventions aimed at mitigating the adverse outcomes associated with semen inflammation.

本文综述了精液炎症在精子质量、胚胎着床、胎盘着床中的重要作用及其对生殖健康的广泛影响。男性生殖道慢性炎症越来越被认为是导致不育的一个重要因素。这种炎症不仅会损害精液质量，还会破坏男性和女性生殖道之间复杂的免疫交流，而这对成功植入、胎盘和怀孕至关重要。本文综述了精液中的炎症介质影响女性免疫环境的机制，从而改变子宫容受性、胎盘形成和胚胎着床。此外，这些干扰对后代的健康和发育的影响进行了讨论，强调了男性生殖道炎症的跨代影响。通过对动物模型和人类研究的研究，本综述强调需要更深入地了解生殖生物学中的免疫相互作用，以及旨在减轻与精液炎症相关的不良后果的新型治疗干预措施的潜力。

{"title":"Effects of semen inflammation on embryo implantation, placentation, pregnancy outcomes and offspring health","authors":"María S. Martinez , Yair A. Chocobar , Yamila Fariz , Daniela A. Paira , Virginia E. Rivero , Rubén D. Motrich","doi":"10.1016/j.placenta.2025.02.002","DOIUrl":"10.1016/j.placenta.2025.02.002","url":null,"abstract":"<div><div>This review explores the critical role of semen inflammation in sperm quality, embryo implantation<span>, placentation<span>, and its broader implications on reproductive health<span><span><span>. Chronic inflammation of the male genital tract has been increasingly recognized as a significant factor contributing to infertility. This inflammation not only impairs semen quality but also disrupts the intricate immune cross-talk between the male and female genital tracts, which is essential for successful implantation, </span>placentation<span><span> and pregnancy. The review synthesizes existing research on the mechanisms by which inflammatory mediators in semen influence the female immune environment, leading to altered uterine receptivity, placental formation, and </span>embryo implantation. Furthermore, the impact of these disruptions on the health and development of the offspring is discussed, highlighting the transgenerational effects of male genital tract inflammation. Through an examination of both animal models and human studies, this review underscores the need for a deeper understanding of the immune interactions in </span></span>reproductive biology<span> and the potential for novel therapeutic interventions aimed at mitigating the adverse outcomes associated with semen inflammation.</span></span></span></span></div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"173 ","pages":"Pages 140-152"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143409918","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

Placental Privilege: Evidence of organ resilience in severe COVID-19 in pregnancy 胎盘特权：重症COVID-19妊娠期器官恢复能力的证据。

IF 2.5 2区医学 Q2 DEVELOPMENTAL BIOLOGY

Placenta

Pub Date : 2026-01-01 DOI: 10.1016/j.placenta.2025.05.003

Pietro Presicce , Marco Morselli , Anhyo Jeong , Marie Altendahl , Guadalupe Martinez , Giorgia Del Vecchio , Sherin U. Devaskar , Matteo Pellegrini , Yalda Afshar , Suhas G. Kallapur

Background

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.

Methods

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.

Results

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.

Conclusion

Despite multi-organ failure, severe COVID-19 did not significantly impact placental function and transcriptomics with iatrogenic preterm birth indicated for maternal-indications.

背景：妊娠期COVID-19感染与早产和重症风险增加相关，需要重症监护入院治疗孕产妇多器官功能衰竭。胎盘是胎儿器官，在母体界面起屏障作用，表达SARS-CoV-2病毒受体。然而，胎盘感染和病毒经胎盘转移是罕见的，提示胎盘抵抗病毒感染。在这里，我们试图确定严重的COVID-19感染对孕产妇、新生儿和胎盘结局的影响。方法：回顾性分析某四期围产期学术中心前瞻性招募的新冠肺炎孕妇队列（n = 204）。妊娠期间应用脐动脉（UA）多普勒评估胎盘功能。分娩时，评估母体和胎儿的结局，收集配对的母体外周血和胎盘样本（n = 26）进行大量RNA测序（RNA-seq）。测序后进行单细胞反褶积分析和通路分析。结果：重度、无症状或轻/中度COVID-19感染中母亲指征早产发生率较高。重症COVID-19患者UA多普勒评估正常。两组间胎儿生长受限率和胎盘：出生体重比相似。RNA-seq在外周血中显示出明显的适应性免疫激活特征，而胎盘转录本在免疫细胞类型上没有显著变化。结论：尽管存在多器官功能衰竭，但重症COVID-19对医源性早产患者的胎盘功能和转录组学没有显著影响。

{"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":"10.1016/j.placenta.2025.05.003","url":null,"abstract":"<div><h3>Background</h3><div><span>COVID-19 infection in pregnancy is associated with preterm birth<span> and an increased risk of severe disease, needing intensive care admission for management of maternal multi-organ failure. The placenta, a </span></span>fetal organ<span><span>, functions as a barrier at the maternal interface and expresses the SARS-CoV-2 viral receptors. However, placental infection and </span>transplacental transfer<span> 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.</span></span></div></div><div><h3>Methods</h3><div><span>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 </span>placental function<span>. 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.</span></div></div><div><h3>Results</h3><div>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<span> 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.</span></div></div><div><h3>Conclusion</h3><div>Despite multi-organ failure, severe COVID-19 did not significantly impact placental function and transcriptomics<span> with iatrogenic preterm birth indicated for maternal-indications.</span></div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"173 ","pages":"Pages 78-86"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","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}

引用次数: 0

Intercellular adhesion molecule (ICAM)-1 is required to control Toxoplasma gondii infection in uterine tissues and establish a successful gestation in a murine model of congenital toxoplasmosis 细胞间黏附分子(ICAM)-1是控制刚地弓形虫在子宫组织感染和建立小鼠先天性弓形虫病模型成功妊娠所必需的。

IF 2.5 2区医学 Q2 DEVELOPMENTAL BIOLOGY

Placenta

Pub Date : 2026-01-01 DOI: 10.1016/j.placenta.2025.04.002

Rafaela José da Silva , Marcos Paulo Oliveira Almeida , Angelica Oliveira Gomes , Priscila Silva Franco , Guilherme de Souza , Alessandra Monteiro Rosini , Iliana Claudia Balga Milian , João Paulo Silva Servato , José Roberto Mineo , Tiago Wilson Patriarca Mineo , Neide Maria Silva , Eloisa Amália Vieira Ferro , Bellisa Freitas Barbosa

The placenta acts as a critical barrier against pathogens during pregnancy, although Toxoplasma gondii can breach this defense, leading to congenital infections. Intercellular adhesion molecule-1 (ICAM-1) is an adhesion molecule involved in immune responses, including leukocyte recruitment and pathogen clearance. Here, we investigate the role of ICAM-1 in gestational success and T. gondii infection using wild-type (WT) and ICAM-1 knockout (ICAM-1^−/−) mice across early, mid- and late pregnancy stages. In early pregnancy, ICAM-1^−/− mice infected with T. gondii exhibited a significantly higher embryonic loss rate (63 %) compared to WT mice (5 %). This was accompanied by an increased parasite burden in uterine tissues and elevated systemic and local IFN-γ levels, despite a reduced local inflammatory response. In contrast, mid-pregnancy showed no significant differences in fetal loss or implantation success among groups, suggesting ICAM-1 plays a limited role at this stage. During late pregnancy, ICAM-1^−/− mice experienced higher embryonic loss rates (40 %) compared to WT mice (26.2 %), along with reduced implantation success and elevated IFN-γ levels, though parasite burden remained unchanged. Histological analysis revealed a less severe inflammatory profile in infected ICAM-1^−/− uterine tissues, marked by reduced necrosis and hyperemia compared to WT mice. FOXP3 expression, a marker of regulatory T cells, was unaffected by ICAM-1, although a trend towards reestablishment was observed in infected ICAM-1^−/− mice. Our findings underscore the critical role of ICAM-1 in ensuring gestational success during T. gondii infection, particularly in early pregnancy, by modulating immune responses at the maternal-fetal interface.

胎盘在怀孕期间是抵御病原体的关键屏障，尽管刚地弓形虫可以破坏这一防御，导致先天性感染。细胞间粘附分子-1 （ICAM-1）是一种参与免疫应答的粘附分子，包括白细胞募集和病原体清除。在这里，我们使用野生型（WT）和ICAM-1敲除（icam -/-）小鼠在妊娠早期、中期和晚期研究了ICAM-1在妊娠成功和弓形虫感染中的作用。在妊娠早期，感染弓形虫的ICAM-1-/-小鼠的胚胎损失率（63%）明显高于WT小鼠（5%）。这伴随着子宫组织中寄生虫负担的增加以及全身和局部IFN-γ水平的升高，尽管局部炎症反应减少。相比之下，妊娠中期各组胎儿丢失和着床成功率无显著差异，提示ICAM-1在该阶段的作用有限。在妊娠后期，ICAM-1-/-小鼠的胚胎损失率（40%）高于WT小鼠（26.2%），同时植入成功率降低，IFN-γ水平升高，但寄生虫负担保持不变。组织学分析显示，与WT小鼠相比，感染ICAM-1-/-子宫组织的炎症程度较轻，其特征是坏死和充血减少。作为调节性T细胞的标志，FOXP3的表达不受ICAM-1的影响，尽管在感染ICAM-1-/-的小鼠中观察到重建的趋势。我们的研究结果强调了ICAM-1在弓形虫感染期间，特别是在妊娠早期，通过调节母胎界面的免疫反应，在确保妊娠成功方面的关键作用。

{"title":"Intercellular adhesion molecule (ICAM)-1 is required to control Toxoplasma gondii infection in uterine tissues and establish a successful gestation in a murine model of congenital toxoplasmosis","authors":"Rafaela José da Silva , Marcos Paulo Oliveira Almeida , Angelica Oliveira Gomes , Priscila Silva Franco , Guilherme de Souza , Alessandra Monteiro Rosini , Iliana Claudia Balga Milian , João Paulo Silva Servato , José Roberto Mineo , Tiago Wilson Patriarca Mineo , Neide Maria Silva , Eloisa Amália Vieira Ferro , Bellisa Freitas Barbosa","doi":"10.1016/j.placenta.2025.04.002","DOIUrl":"10.1016/j.placenta.2025.04.002","url":null,"abstract":"<div><div>The placenta acts as a critical barrier against pathogens during pregnancy, although <span><span>Toxoplasma gondii</span></span><span><span> can breach this defense, leading to congenital infections<span>. Intercellular adhesion molecule-1 (ICAM-1) is an adhesion molecule<span> involved in immune responses, including leukocyte recruitment and </span></span></span>pathogen clearance. Here, we investigate the role of ICAM-1 in gestational success and </span><em>T. gondii</em> infection using wild-type (WT) and ICAM-1 knockout (ICAM-1<sup>−/−</sup><span>) mice across early, mid- and late pregnancy<span> stages. In early pregnancy, ICAM-1</span></span><sup>−/−</sup> mice infected with <em>T. gondii</em><span><span> exhibited a significantly higher embryonic loss rate (63 %) compared to WT mice (5 %). This was accompanied by an increased parasite burden in uterine tissues and elevated systemic and local IFN-γ levels, despite a reduced local </span>inflammatory response<span>. In contrast, mid-pregnancy showed no significant differences in fetal loss or implantation success among groups, suggesting ICAM-1 plays a limited role at this stage. During late pregnancy, ICAM-1</span></span><sup>−/−</sup> mice experienced higher embryonic loss rates (40 %) compared to WT mice (26.2 %), along with reduced implantation success and elevated IFN-γ levels, though parasite burden remained unchanged. Histological analysis revealed a less severe inflammatory profile in infected ICAM-1<sup>−/−</sup><span><span><span> uterine tissues, marked by reduced necrosis and hyperemia compared to WT mice. </span>FOXP3 expression, a marker of </span>regulatory T cells, was unaffected by ICAM-1, although a trend towards reestablishment was observed in infected ICAM-1</span><sup>−/−</sup> mice. Our findings underscore the critical role of ICAM-1 in ensuring gestational success during <em>T. gondii</em> infection, particularly in early pregnancy, by modulating immune responses at the maternal-fetal interface.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"173 ","pages":"Pages 50-62"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035393","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

The POHaD paradigm: role of the placenta in paternal programming POHaD范式：胎盘在父系编程中的作用。

IF 2.5 2区医学 Q2 DEVELOPMENTAL BIOLOGY

Placenta

Pub Date : 2026-01-01 DOI: 10.1016/j.placenta.2025.04.027

Evangelina Capobianco , Irune Pirrone

The Paternal Origins of Health and Disease (POHaD) paradigm emerges from the well-known Developmental Origins of Health and Disease (DOHaD) concept. Research into the programming of metabolic diseases originating from the paternal germline began over 20 years ago, focusing on the father's pre-conceptional exposure, such as metabolic disorders and lifestyle habits (kind of diet, exercise, smoking, drugs consumption, etc.). This exposure can lead to epigenetic marks not only in his germ cells but also in other components of the semen that impact the health of future generations.

The significant role of the paternal genome in the fetal component of the placenta and the recognition of the placenta's involvement in postnatal disease programming underscore the importance of studying the placenta in paternal programming research. The aim of this work is to review what we know so far about paternal programming highlighting the variations in the phenotype of the placenta and the influence of it in the programming of metabolic pathologies in the offspring of fathers exposed to metabolic disorders such as obesity and diabetes.

健康和疾病的父系起源（POHaD）范式是从众所周知的健康和疾病的发育起源（DOHaD）概念中产生的。对源自父亲生殖系的代谢性疾病编程的研究始于20多年前，重点关注父亲孕前暴露，如代谢性疾病和生活习惯（饮食、运动、吸烟、吸毒等）。这种暴露不仅会在他的生殖细胞中，而且会在精液的其他成分中导致影响后代健康的表观遗传标记。父系基因组在胎盘的胎儿成分中的重要作用以及胎盘参与产后疾病规划的认识强调了研究胎盘在父系规划研究中的重要性。这项工作的目的是回顾迄今为止我们所知道的关于父亲程序的内容，强调胎盘表型的变化，以及它对暴露于代谢紊乱（如肥胖和糖尿病）的父亲后代代谢病理程序的影响。

{"title":"The POHaD paradigm: role of the placenta in paternal programming","authors":"Evangelina Capobianco , Irune Pirrone","doi":"10.1016/j.placenta.2025.04.027","DOIUrl":"10.1016/j.placenta.2025.04.027","url":null,"abstract":"<div><div><span>The Paternal Origins of Health and Disease (POHaD) paradigm emerges from the well-known Developmental Origins of Health and Disease (DOHaD) concept. Research into the programming of metabolic diseases originating from the paternal </span>germline<span> began over 20 years ago, focusing on the father's pre-conceptional exposure, such as metabolic disorders and lifestyle habits (kind of diet, exercise, smoking, drugs consumption, etc.). This exposure can lead to epigenetic marks not only in his germ cells but also in other components of the semen that impact the health of future generations.</span></div><div>The significant role of the paternal genome in the fetal component of the placenta and the recognition of the placenta's involvement in postnatal disease programming underscore the importance of studying the placenta in paternal programming research. The aim of this work is to review what we know so far about paternal programming highlighting the variations in the phenotype of the placenta and the influence of it in the programming of metabolic pathologies in the offspring of fathers exposed to metabolic disorders such as obesity and diabetes.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"173 ","pages":"Pages 160-165"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064544","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