Pub Date : 2026-01-29DOI: 10.1016/j.placenta.2026.01.019
Lindsay S Cahill, Sarah Debebe, Jessica Peng, John G Sled
Our understanding of the structure and function of the placenta and of placental disease have been enhanced by the use of in vivo imaging technologies and rodent models of pregnancy. These technologies share similarities with those used in the clinic to assess and diagnose complications of human pregnancies, providing an easy pathway for advances in rodent imaging and the findings from rodent studies to be translated to humans. Here, we review the available in vivo imaging technologies used in rodent studies of the placenta including magnetic resonance, ultrasound, positron emission tomography, and optical techniques. We synthesize the studies that have used these techniques to investigate placental perfusion, microvascular imaging, metabolism and structure. We also discuss the benefits and limitations of the technologies and provide future directions based on gaps in the present knowledge and limitations of the techniques.
{"title":"In vivo imaging of the rodent placenta.","authors":"Lindsay S Cahill, Sarah Debebe, Jessica Peng, John G Sled","doi":"10.1016/j.placenta.2026.01.019","DOIUrl":"https://doi.org/10.1016/j.placenta.2026.01.019","url":null,"abstract":"<p><p>Our understanding of the structure and function of the placenta and of placental disease have been enhanced by the use of in vivo imaging technologies and rodent models of pregnancy. These technologies share similarities with those used in the clinic to assess and diagnose complications of human pregnancies, providing an easy pathway for advances in rodent imaging and the findings from rodent studies to be translated to humans. Here, we review the available in vivo imaging technologies used in rodent studies of the placenta including magnetic resonance, ultrasound, positron emission tomography, and optical techniques. We synthesize the studies that have used these techniques to investigate placental perfusion, microvascular imaging, metabolism and structure. We also discuss the benefits and limitations of the technologies and provide future directions based on gaps in the present knowledge and limitations of the techniques.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132885","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}
Pub Date : 2026-01-29DOI: 10.1016/j.placenta.2026.01.017
Yang Zhang, Di Wu, Li Zou, Xiangwei Cheng, Xiaoxia Liu
Background
Preeclampsia (PE) causes maternal and perinatal morbidity through defective placental vascularization. Autophagy enhances placental mesenchymal stem/stromal cells (PMSC) proangiogenic properties while autophagy is reduced in PE. Long non-coding RNA GAS5, elevated in PE placenta, suppresses endothelial angiogenesis. N6-methyladenosine (m6A) modification through METTL3 regulates RNA stability and autophagy. However, regulatory mechanisms governing PMSC autophagy in PE remain unclear.
Method
Placenta specimens and PMSC from the normal and PE were compared. Molecular analyses included qRT-PCR, Western blotting, and m6A level evaluation. Transfections used siRNA knockdown and plasmid overexpression with rescue experiments. Autophagy was evaluated through LC3-II/LC3-I ratios and p62. Cellular functional assessments comprised CKK8 assays, ELISA for VEGF secretion, and tube formation for angiogenesis. MeRIP-PCR, RNA pull-down assay and RNA immunoprecipitation PCR identified m6A-modified transcripts.
Result
PE placenta and PMSC demonstrated significantly reduced METTL3 expression and global m6A modification levels, accompanied by elevated GAS5 expression. METTL3 overexpression enhanced PMSC autophagy, cell proliferation, VEGF secretion, and angiogenic capacity, while GAS5 exhibited opposing effects. GAS5 knockdown rescued PMSC autophagy and dysfunction caused by METTL3 deficiency. Mechanistically, METTL3 catalyzed m6A modification of GAS5 transcripts, facilitating YTHDF3-mediated recognition and degradation. YTHDF3 depletion reversed METTL3-induced autophagy improvements, confirming the regulatory cascade.
Conclusion
Our findings establish a novel epigenetic regulatory network wherein METTL3/YTHDF3-mediated GAS5 degradation controls PMSC autophagy in PE. This pathway represents a potential therapeutic target for ameliorating placental vascularization defects in PE.
{"title":"METTL3-regulated m6A modification modulates autophagy of placental mesenchymal stem/stromal cell by YTHDF3-mediated degradation of LncRNA GAS5 in preeclampsia","authors":"Yang Zhang, Di Wu, Li Zou, Xiangwei Cheng, Xiaoxia Liu","doi":"10.1016/j.placenta.2026.01.017","DOIUrl":"10.1016/j.placenta.2026.01.017","url":null,"abstract":"<div><h3>Background</h3><div>Preeclampsia (PE) causes maternal and perinatal morbidity through defective placental vascularization. Autophagy enhances placental mesenchymal stem/stromal cells (PMSC) proangiogenic properties while autophagy is reduced in PE. Long non-coding RNA GAS5, elevated in PE placenta, suppresses endothelial angiogenesis. N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) modification through METTL3 regulates RNA stability and autophagy. However, regulatory mechanisms governing PMSC autophagy in PE remain unclear.</div></div><div><h3>Method</h3><div>Placenta specimens and PMSC from the normal and PE were compared. Molecular analyses included qRT-PCR, Western blotting, and m<sup>6</sup>A level evaluation. Transfections used siRNA knockdown and plasmid overexpression with rescue experiments. Autophagy was evaluated through LC3-II/LC3-I ratios and p62. Cellular functional assessments comprised CKK8 assays, ELISA for VEGF secretion, and tube formation for angiogenesis. MeRIP-PCR, RNA pull-down assay and RNA immunoprecipitation PCR identified m<sup>6</sup>A-modified transcripts.</div></div><div><h3>Result</h3><div>PE placenta and PMSC demonstrated significantly reduced METTL3 expression and global m<sup>6</sup>A modification levels, accompanied by elevated GAS5 expression. METTL3 overexpression enhanced PMSC autophagy, cell proliferation, VEGF secretion, and angiogenic capacity, while GAS5 exhibited opposing effects. GAS5 knockdown rescued PMSC autophagy and dysfunction caused by METTL3 deficiency. Mechanistically, METTL3 catalyzed m<sup>6</sup>A modification of GAS5 transcripts, facilitating YTHDF3-mediated recognition and degradation. YTHDF3 depletion reversed METTL3-induced autophagy improvements, confirming the regulatory cascade.</div></div><div><h3>Conclusion</h3><div>Our findings establish a novel epigenetic regulatory network wherein METTL3/YTHDF3-mediated GAS5 degradation controls PMSC autophagy in PE. This pathway represents a potential therapeutic target for ameliorating placental vascularization defects in PE.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"176 ","pages":"Pages 31-42"},"PeriodicalIF":2.5,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146181749","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}
Pub Date : 2026-01-28DOI: 10.1016/j.placenta.2026.01.018
Gudrun Meinhardt , Hanna Waldhäusl , Leila Saleh , Sandra Haider , Jürgen Pollheimer , Christian Fiala , Dieter Bettelheim , Johanna Gamauf , Matthias Postl , Matthias Wieser , Regina Grillari-Voglauer , Martin Knöfler
Herein, we molecularly characterize the novel human term trophoblast cell line TB/SVTERT350 and show that it meets the criteria for trophoblast identity and subtype specification. TB/SVTERT350, cultured under stemness conditions in 2D or 3D, express trophoblast progenitor markers such as E-cadherin, TEAD4 and YAP1 and develop into CGβ-producing syncytiotrophoblast and HLA-G-expressing extravillous trophoblasts in the respective differentiation media. Expanding TB/SVTERT350 organoids share structural similarities with primary trophoblast organoids and express NOTCH1 suggesting that the cell line exhibits phenotypic traits of proximal cell column trophoblasts. In summary, TB/SVTERT350 could represent a reliable model for studying mechanisms of placental growth and differentiation.
{"title":"Characterization, organoid formation and differentiation potential of the novel term trophoblast cell line TB/SVTERT350","authors":"Gudrun Meinhardt , Hanna Waldhäusl , Leila Saleh , Sandra Haider , Jürgen Pollheimer , Christian Fiala , Dieter Bettelheim , Johanna Gamauf , Matthias Postl , Matthias Wieser , Regina Grillari-Voglauer , Martin Knöfler","doi":"10.1016/j.placenta.2026.01.018","DOIUrl":"10.1016/j.placenta.2026.01.018","url":null,"abstract":"<div><div>Herein, we molecularly characterize the novel human term trophoblast cell line TB/SVTERT350 and show that it meets the criteria for trophoblast identity and subtype specification. TB/SVTERT350, cultured under stemness conditions in 2D or 3D, express trophoblast progenitor markers such as E-cadherin, TEAD4 and YAP1 and develop into CGβ-producing syncytiotrophoblast and HLA-G-expressing extravillous trophoblasts in the respective differentiation media. Expanding TB/SVTERT350 organoids share structural similarities with primary trophoblast organoids and express NOTCH1 suggesting that the cell line exhibits phenotypic traits of proximal cell column trophoblasts. In summary, TB/SVTERT350 could represent a reliable model for studying mechanisms of placental growth and differentiation.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"175 ","pages":"Pages 73-77"},"PeriodicalIF":2.5,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119954","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}
By directly regulating nutrient supply and fetal growth, the placenta plays a central role in fetal programming. The extent to which SARS-CoV-2 maternal infection during pregnancy will affect the long-term metabolic health of the newborn is yet to be explored. As trophoblast cells express the ACE2 (angiotensin converting enzyme 2) receptor, we aimed to investigate the potential fetal programming effects of SARS-CoV-2 Spike protein S1 subunit (Spike S1), by focusing on nutrient transport.
Methods
We investigated the in vitro effect of Spike S1 (100 ng/mL; 24 h) on two in vitro models of human trophoblasts, primary cultured human trophoblasts and the BeWo cell line.
Results
Spike S1 elicited an inflammatory response, caused a low grade cytotoxic and antiproliferative effect and, in the more actively replicating BeWo cell line, induced G2-M cell cycle arrest. Moreover, it interfered with the activities of the glucose transporter GLUT1 (facilitative glucose transporter 1) and the folic acid transporter RFC1 (reduced folate carrier 1), and altered the gene expression of the amino acid transporters LAT1 (L-type amino acid transporter 1) and y+LAT2 (y+L-type amino acid transporter 2). It also markedly increased mTOR (mammalian target of rapamycin) gene expression in primary cultured trophoblasts.
Discussion
We conclude that the Spike S1 subunit induces some changes in trophoblast metabolic parameters that may be of relevance for fetal programming metabolic disease in the adult.
{"title":"In vitro exposure to the SARS-CoV-2 Spike protein subunit S1 leads to changes in several functional characteristics of human trophoblast cells","authors":"Francisca Carmo , Ilda Rodrigues , Carla Ramalho , Fátima Martel","doi":"10.1016/j.placenta.2026.01.015","DOIUrl":"10.1016/j.placenta.2026.01.015","url":null,"abstract":"<div><h3>Introduction</h3><div>By directly regulating nutrient supply and fetal growth, the placenta plays a central role in fetal programming. The extent to which SARS-CoV-2 maternal infection during pregnancy will affect the long-term metabolic health of the newborn is yet to be explored. As trophoblast cells express the ACE2 (angiotensin converting enzyme 2) receptor, we aimed to investigate the potential fetal programming effects of SARS-CoV-2 Spike protein S1 subunit (Spike S1), by focusing on nutrient transport.</div></div><div><h3>Methods</h3><div>We investigated the <em>in vitro</em> effect of Spike S1 (100 ng/mL; 24 h) on two <em>in vitro</em> models of human trophoblasts, primary cultured human trophoblasts and the BeWo cell line.</div></div><div><h3>Results</h3><div>Spike S1 elicited an inflammatory response, caused a low grade cytotoxic and antiproliferative effect and, in the more actively replicating BeWo cell line, induced G2-M cell cycle arrest. Moreover, it interfered with the activities of the glucose transporter GLUT1 (facilitative glucose transporter 1) and the folic acid transporter RFC1 (reduced folate carrier 1), and altered the gene expression of the amino acid transporters LAT1 (L-type amino acid transporter 1) and y<sup>+</sup>LAT2 (y<sup>+</sup>L-type amino acid transporter 2). It also markedly increased mTOR (mammalian target of rapamycin) gene expression in primary cultured trophoblasts.</div></div><div><h3>Discussion</h3><div>We conclude that the Spike S1 subunit induces some changes in trophoblast metabolic parameters that may be of relevance for fetal programming metabolic disease in the adult.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"175 ","pages":"Pages 40-53"},"PeriodicalIF":2.5,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146080313","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}
Pub Date : 2026-01-21DOI: 10.1016/j.placenta.2026.01.013
Dianjie Li , Jiayi Jiang , Yixiang Zhong , Manling Luo , Jianhong Chen , Jing Li , Xiangli Chen , Meng Li , Mei Zhong , Yi Zhang
Introduction
Fetal growth restriction (FGR) is one of the most common perinatal complications. The specific molecular mechanism remains undefined. N6-methyladenosine (m6A), the most common RNA modification in eukaryotes, is known to be associated with a variety of diseases. However, the relationships among METTL3, m6A and FGR have not been clearly reported.
Methods
The expression of METTL3, downstream target-leptin receptor (LEPR) and m6A modification level were compared between placentas of FGR and those of normal pregnancies. C57BL/6 pregnant mice were intraperitoneally injected with the METTL3-specific inhibitor STM2457 to analyze the effects of METTL3-associated m6A methylation. Changes downstream of METTL3 were determined by RNA sequencing. The regulatory relationships among METTL3, m6A, and LEPR were explored by cell migration assay, invasion assay, CCK8 assay, Western blotting and MeRIP‒qPCR.
Results
METTL3, LEPR and m6A modification were significantly decreased in the placenta of patients with FGR. After STM2457 treatment, adverse pregnancy outcomes and the FGR phenotype of fetal mice were observed. RNA-seq revealed that the downstream target of METTL3 was LEPR. The expression of LEPR was positively correlated with that of METTL3 via in vitro cellular mechanism experiments. The m6A modification level of LEPR was decreased when METTL3 was knocked down and increased when METTL3 was overexpressed. Furthermore, METTL3 and LEPR can separately or collectively promote the proliferation, migration and invasion of trophoblasts likely through m6A modification.
Discussion
Our study revealed that METTL3 regulated trophoblastic function likely through an m6A-LEPR-dependent mechanism in HTR8/SVneo cells and identified a potential biomarker panel for treatment prediction in FGR.
{"title":"METTL3-mediated N6-methyladenosine modification of LEPR is critical for fetal growth restriction","authors":"Dianjie Li , Jiayi Jiang , Yixiang Zhong , Manling Luo , Jianhong Chen , Jing Li , Xiangli Chen , Meng Li , Mei Zhong , Yi Zhang","doi":"10.1016/j.placenta.2026.01.013","DOIUrl":"10.1016/j.placenta.2026.01.013","url":null,"abstract":"<div><h3>Introduction</h3><div>Fetal growth restriction (FGR) is one of the most common perinatal complications. The specific molecular mechanism remains undefined. N6-methyladenosine (m<sup>6</sup>A), the most common RNA modification in eukaryotes, is known to be associated with a variety of diseases. However, the relationships among METTL3, m<sup>6</sup>A and FGR have not been clearly reported.</div></div><div><h3>Methods</h3><div>The expression of METTL3, downstream target-leptin receptor (LEPR) and m<sup>6</sup>A modification level were compared between placentas of FGR and those of normal pregnancies. C57BL/6 pregnant mice were intraperitoneally injected with the METTL3-specific inhibitor STM2457 to analyze the effects of METTL3-associated m<sup>6</sup>A methylation. Changes downstream of METTL3 were determined by RNA sequencing. The regulatory relationships among METTL3, m<sup>6</sup>A, and LEPR were explored by cell migration assay, invasion assay, CCK8 assay, Western blotting and MeRIP‒qPCR.</div></div><div><h3>Results</h3><div>METTL3, LEPR and m<sup>6</sup>A modification were significantly decreased in the placenta of patients with FGR. After STM2457 treatment, adverse pregnancy outcomes and the FGR phenotype of fetal mice were observed. RNA-seq revealed that the downstream target of METTL3 was LEPR. The expression of LEPR was positively correlated with that of METTL3 via in vitro cellular mechanism experiments. The m<sup>6</sup>A modification level of LEPR was decreased when METTL3 was knocked down and increased when METTL3 was overexpressed. Furthermore, METTL3 and LEPR can separately or collectively promote the proliferation, migration and invasion of trophoblasts likely through m<sup>6</sup>A modification.</div></div><div><h3>Discussion</h3><div>Our study revealed that METTL3 regulated trophoblastic function likely through an m<sup>6</sup>A-LEPR-dependent mechanism in HTR8/SVneo cells and identified a potential biomarker panel for treatment prediction in FGR.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"175 ","pages":"Pages 54-65"},"PeriodicalIF":2.5,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146080312","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}
Pub Date : 2026-01-20DOI: 10.1016/j.placenta.2026.01.014
Yajing Mao , Jialu Xu , Shengyi Gu , Huanrong Liu , Sheng Wan , Xiping Hong , Jiejun Cheng , Xiaolin Hua
Objective
Our aim was to evaluate placental function using IVIM diffusion-weighted MRI in both normal pregnancies and gestational hypertension, and develop a combined predictive model for severe fetal growth restriction (sFGR).
Method
We studied 32 healthy pregnant women and 40 with gestational hypertension (20 with sFGR, 20 without). Five IVIM-based parameters were calculated: perfusion fraction (f), true diffusion coefficient (D), pseudo-diffusion coefficient (D∗), diffusion distribution coefficient (DDC), and superdiffusion index (γ). These parameters were compared between the groups. Predictive efficiency was evaluated using logistic regression analysis and receiver operating characteristic (ROC) curve analysis.
Results
Compared to controls, gestational hypertension cases exhibited lower f, D, DDC values and higher γ value (all p < 0.05). Both f value (OR: 0.257, 95 % CI: 0.069–0.957; p = 0.043) and γ value (OR: 0.343, 95 % CI: 0.128–0.918; p = 0.033) independently predicted sFGR. A combined predictive model (f, D∗, DDC and γ) achieved superior prediction (AUC: 0.838).
Conclusion
IVIM-derived parameters effectively quantify placental microcirculation differences and show strong potential as non-invasive biomarkers for sFGR prediction in gestational hypertension.
{"title":"In vivo assessment of placental microstructure in normal pregnancy and gestational hypertension: An IVIM-based MRI study","authors":"Yajing Mao , Jialu Xu , Shengyi Gu , Huanrong Liu , Sheng Wan , Xiping Hong , Jiejun Cheng , Xiaolin Hua","doi":"10.1016/j.placenta.2026.01.014","DOIUrl":"10.1016/j.placenta.2026.01.014","url":null,"abstract":"<div><h3>Objective</h3><div>Our aim was to evaluate placental function using IVIM diffusion-weighted MRI in both normal pregnancies and gestational hypertension, and develop a combined predictive model for severe fetal growth restriction (sFGR).</div></div><div><h3>Method</h3><div>We studied 32 healthy pregnant women and 40 with gestational hypertension (20 with sFGR, 20 without). Five IVIM-based parameters were calculated: perfusion fraction (f), true diffusion coefficient (D), pseudo-diffusion coefficient (D∗), diffusion distribution coefficient (DDC), and superdiffusion index (γ). These parameters were compared between the groups. Predictive efficiency was evaluated using logistic regression analysis and receiver operating characteristic (ROC) curve analysis.</div></div><div><h3>Results</h3><div>Compared to controls, gestational hypertension cases exhibited lower f, D, DDC values and higher γ value (all p < 0.05). Both f value (OR: 0.257, 95 % CI: 0.069–0.957; p = 0.043) and γ value (OR: 0.343, 95 % CI: 0.128–0.918; p = 0.033) independently predicted sFGR. A combined predictive model (f, D∗, DDC and γ) achieved superior prediction (AUC: 0.838).</div></div><div><h3>Conclusion</h3><div>IVIM-derived parameters effectively quantify placental microcirculation differences and show strong potential as non-invasive biomarkers for sFGR prediction in gestational hypertension.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"175 ","pages":"Pages 33-39"},"PeriodicalIF":2.5,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146039564","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}
Pub Date : 2026-01-17DOI: 10.1016/j.placenta.2026.01.011
Jana Pastuschek , Daniela Wissenbach , Udo R. Markert , Janine Zoellkau , Ekkehard Schleussner , Frank T. Peters , Tanja Groten
Introduction
Bacterial infections during pregnancy can endanger both mother and fetus, leading to premature rupture of membranes, chorioamnionitis, preterm birth, and neonatal sepsis. Effective antibiotic therapy must ensure sufficient exposure. Ampicillin is widely used in pregnancy, particularly against group B streptococcus (GBS) and E. coli, but its pharmacokinetics, including placental transfer, are not fully understood. This study evaluated ampicillin's transplacental transfer using an ex vivo placenta dual-side perfusion model and assessed maternal serum concentrations in pregnant women undergoing therapy.
Materials and methods
Six placentas were perfused with 50 or 100 mg/L ampicillin. Ampicillin concentrations were assessed both in the maternal and fetal circuits every 30 min during a period of 4 h. Additionally, maternal serum samples from six pregnant women (gestational age: 24 + 4 to 33 + 0) receiving 2 g ampicillin intravenously were analyzed every 30 min up to 4 h post-administration. Antibiotic concentrations were determined using LC-MS.
Results
Concentrations determined in the maternal perfusion circuit were 33.4 ± 15.9 and 41.2 ± 5.8 mg/L, as well as 15.4 ± 4.5 and 25.3 ± 19.9 mg/L in the fetal circuit. The transfer rate was about 25 % after 4 h of perfusion. Maternal serum concentrations at 30 min reached 54.1 ± 6.4 mg/L and declined to 2.3 ± 1.6 mg/L at 4 h.
Discussion
This study using an ex vivo placenta perfusion model, revealed only moderate transplacental transfer of ampicillin. This finding, in the context of the retrieved serum concentrations, suggests that adjusted dosing may be required in severe conditions to optimize drug exposure, emphasizing the need for further pharmacokinetic research in pregnancy.
{"title":"Transplacental passage of ampicillin: Implications for antenatal therapy","authors":"Jana Pastuschek , Daniela Wissenbach , Udo R. Markert , Janine Zoellkau , Ekkehard Schleussner , Frank T. Peters , Tanja Groten","doi":"10.1016/j.placenta.2026.01.011","DOIUrl":"10.1016/j.placenta.2026.01.011","url":null,"abstract":"<div><h3>Introduction</h3><div>Bacterial infections during pregnancy can endanger both mother and fetus, leading to premature rupture of membranes, chorioamnionitis, preterm birth, and neonatal sepsis. Effective antibiotic therapy must ensure sufficient exposure. Ampicillin is widely used in pregnancy, particularly against group B <em>streptococcus</em> (GBS) and <em>E. coli</em>, but its pharmacokinetics, including placental transfer, are not fully understood. This study evaluated ampicillin's transplacental transfer using an <em>ex vivo</em> placenta dual-side perfusion model and assessed maternal serum concentrations in pregnant women undergoing therapy.</div></div><div><h3>Materials and methods</h3><div>Six placentas were perfused with 50 or 100 mg/L ampicillin. Ampicillin concentrations were assessed both in the maternal and fetal circuits every 30 min during a period of 4 h. Additionally, maternal serum samples from six pregnant women (gestational age: 24 + 4 to 33 + 0) receiving 2 g ampicillin intravenously were analyzed every 30 min up to 4 h post-administration. Antibiotic concentrations were determined using LC-MS.</div></div><div><h3>Results</h3><div>Concentrations determined in the maternal perfusion circuit were 33.4 ± 15.9 and 41.2 ± 5.8 mg/L, as well as 15.4 ± 4.5 and 25.3 ± 19.9 mg/L in the fetal circuit. The transfer rate was about 25 % after 4 h of perfusion. Maternal serum concentrations at 30 min reached 54.1 ± 6.4 mg/L and declined to 2.3 ± 1.6 mg/L at 4 h.</div></div><div><h3>Discussion</h3><div>This study using an <em>ex vivo</em> placenta perfusion model, revealed only moderate transplacental transfer of ampicillin. This finding, in the context of the retrieved serum concentrations, suggests that adjusted dosing may be required in severe conditions to optimize drug exposure, emphasizing the need for further pharmacokinetic research in pregnancy.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"175 ","pages":"Pages 66-72"},"PeriodicalIF":2.5,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146120026","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}
Pub Date : 2026-01-17DOI: 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.
{"title":"Neuroplacental Interactions in early human development: Insights from selective acute neuronal necrosis","authors":"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","doi":"10.1016/j.placenta.2026.01.012","DOIUrl":"10.1016/j.placenta.2026.01.012","url":null,"abstract":"<div><h3>Introduction</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div><div>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.</div><div>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 %).</div></div><div><h3>Discussion</h3><div>These findings highlight the close relationship between placental lesions and SANN, supporting the importance of CNS and placental assessment in these autopsies.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"175 ","pages":"Pages 16-24"},"PeriodicalIF":2.5,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030616","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}
Pub Date : 2026-01-16DOI: 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.
{"title":"Structural alterations in the placental villous tree in well-controlled gestational diabetes mellitus","authors":"N. Barapatre , L. Halm , C. Schmitz , F.E. von Koch , C. Kampfer , H-G. Frank","doi":"10.1016/j.placenta.2026.01.010","DOIUrl":"10.1016/j.placenta.2026.01.010","url":null,"abstract":"<div><h3>Introduction</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"175 ","pages":"Pages 25-32"},"PeriodicalIF":2.5,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146039563","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}
Pub Date : 2026-01-16DOI: 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.
{"title":"Exploring placental ultrastructure: A review of electron microscopy techniques and emerging methods for resolving 3D organelle architecture.","authors":"Siddharth Acharya, Eric Hanssen, James C Bouwer, John E Schjenken, Kirsty G Pringle, Roger Smith, Joshua J Fisher","doi":"10.1016/j.placenta.2026.01.009","DOIUrl":"https://doi.org/10.1016/j.placenta.2026.01.009","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146093882","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}
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