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In vitro differentiation of macaque extravillous trophoblasts in a low oxygen environment
IF 3 2区 医学 Q2 DEVELOPMENTAL BIOLOGY Pub Date : 2025-02-25 DOI: 10.1016/j.placenta.2025.02.014
Logan T. Keding , Avery R. Heselton , Emily Ren , Sarah A. Shaw , Michelle R. Koenig , Thaddeus G. Golos , Jenna K. Schmidt

Introduction

Early primate placental development occurs within a low oxygen (O2) environment, whereas in vitro differentiation of trophoblasts is performed at supraphysiologic O2 levels. Macaque trophoblast stem cells (TSCs) are capable of differentiation to extravillous trophoblasts (EVTs) in vitro, yet the morphological heterogeneity observed across cells lines necessitates evaluation of optimal culture conditions. Our objectives were to determine the impact of oxygen on the in vitro differentiation of macaque TSCs and to refine the molecular characterization of TSC-differentiated EVTs.

Methods

Macaque TSCs were differentiated to EVTs in either 20% or 5% O2. Gene and protein expression profiles were compared between TSCs and EVTs and between differentiation conditions. Immunohistochemical analysis was performed on early gestation macaque placental tissues to assess in vivo expression of Ki-67, NCAM1 and monkey chorionic gonadotropin (mCG).

Results

EVTs differentiated in 20% O2 had significantly higher expression of CGA, CGB and NOTCH2 and decreased HIF1A expression compared to those cultured in 5% O2. Regardless of oxygen condition, nearly all EVTs expressed NCAM1 and Mamu-AG, the macaque-specific homolog of human EVT marker HLA-G. In vivo placental expression of NCAM1 was restricted to EVTs within the trophoblastic shell and endovasculature, revealing a macaque EVT marker within the placenta.

Discussion

Reduced oxygen minimally impacted macaque EVT differentiation in vitro. Elevated expression of the endovascular EVT marker NOTCH2 potentially suggests that 20% O2 supported differentiation of more mature EVTs. Altogether, a standard 20% O2 environment supports macaque EVT differentiation in vitro and the results further validate the identity of macaque TSC-differentiated EVTs.
{"title":"In vitro differentiation of macaque extravillous trophoblasts in a low oxygen environment","authors":"Logan T. Keding ,&nbsp;Avery R. Heselton ,&nbsp;Emily Ren ,&nbsp;Sarah A. Shaw ,&nbsp;Michelle R. Koenig ,&nbsp;Thaddeus G. Golos ,&nbsp;Jenna K. Schmidt","doi":"10.1016/j.placenta.2025.02.014","DOIUrl":"10.1016/j.placenta.2025.02.014","url":null,"abstract":"<div><h3>Introduction</h3><div>Early primate placental development occurs within a low oxygen (O<sub>2</sub>) environment, whereas <em>in vitro</em> differentiation of trophoblasts is performed at supraphysiologic O<sub>2</sub> levels. Macaque trophoblast stem cells (TSCs) are capable of differentiation to extravillous trophoblasts (EVTs) <em>in vitro</em>, yet the morphological heterogeneity observed across cells lines necessitates evaluation of optimal culture conditions. Our objectives were to determine the impact of oxygen on the <em>in vitro</em> differentiation of macaque TSCs and to refine the molecular characterization of TSC-differentiated EVTs.</div></div><div><h3>Methods</h3><div>Macaque TSCs were differentiated to EVTs in either 20% or 5% O<sub>2</sub>. Gene and protein expression profiles were compared between TSCs and EVTs and between differentiation conditions. Immunohistochemical analysis was performed on early gestation macaque placental tissues to assess <em>in vivo</em> expression of Ki-67, NCAM1 and monkey chorionic gonadotropin (mCG).</div></div><div><h3>Results</h3><div>EVTs differentiated in 20% O<sub>2</sub> had significantly higher expression of <em>CGA</em>, <em>CGB</em> and <em>NOTCH2</em> and decreased <em>HIF1A</em> expression compared to those cultured in 5% O<sub>2</sub>. Regardless of oxygen condition, nearly all EVTs expressed NCAM1 and Mamu-AG, the macaque-specific homolog of human EVT marker HLA-G. <em>In vivo</em> placental expression of NCAM1 was restricted to EVTs within the trophoblastic shell and endovasculature, revealing a macaque EVT marker within the placenta.</div></div><div><h3>Discussion</h3><div>Reduced oxygen minimally impacted macaque EVT differentiation <em>in vitro</em>. Elevated expression of the endovascular EVT marker <em>NOTCH2</em> potentially suggests that 20% O<sub>2</sub> supported differentiation of more mature EVTs. Altogether, a standard 20% O<sub>2</sub> environment supports macaque EVT differentiation <em>in vitro</em> and the results further validate the identity of macaque TSC-differentiated EVTs.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"163 ","pages":"Pages 16-28"},"PeriodicalIF":3.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526909","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
Risk of preeclampsia and other pregnancy complications in frozen single euploid embryo transfers after natural versus artificial endometrial preparation: A truncated randomized controlled trial
IF 3 2区 医学 Q2 DEVELOPMENTAL BIOLOGY Pub Date : 2025-02-25 DOI: 10.1016/j.placenta.2025.02.016
José Bellver , Ana Del Arco , Antonio Pellicer , Laura Caracena , Vicente Serra , Elena Labarta , Gemma Castillón , Gemma Fernández , Ana Barrio , Israel Ortega , Iria Fernández , Margarita Torres , Agustín Ballesteros , Elkin Muñoz , Javier Marqueta , Marcos Ferrando , Ángel Grañeras , José Luis Bartha , Nicolás Garrido , Juan Antonio García-Velasco

Introduction

To determine for the first time the incidence of preeclampsia and other pregnancy complications according to the mode of endometrial preparation for frozen embryo transfer (FET) in a randomized fashion.

Methods

Women about to undergo FET of a single euploid blastocyst were randomly assigned to a modified natural cycle (MNC) or an artificial cycle (AC). Inclusion criteria were as follows: Caucasian; non-obese; 18–43 years of age; nulliparity; regular menstrual cycles; and autologous oocytes. Exclusion criteria were as follows: uterine alterations; moderate-heavy smokers; gamete donation; and chronic diseases. A pilot sub-study of first-trimester markers of preeclampsia was performed in 60 of the patients.

Results

Of the 1260 patients estimated, 591 met the inclusion criteria and were willing to participate; of these, 306 and 285 were randomly assigned to a MNC or AC, respectively. After exclusion, 242 and 227 patients finally underwent a MNC or AC, resulting in 131 and 103 clinical pregnancies, 121 and 92 live births, and 91 and 70 questionnaires obtained concerning pregnancy complications, respectively. The incidence of preeclampsia was double in the AC group (10.00 % versus 4.39 %), though not significantly different. In the AC group, the prevalence of first trimester bleeding was significantly higher (42.85 % versus 15.38 %), and there was a significant reduction in live birth rates (40.53 % versus 50.00 %) in the per protocol analysis. No differences in early markers of preeclampsia were detected between the two groups.

Discussion

Although this randomized study was truncated, our findings are in accordance with previous reports of a higher risk of preeclampsia and other complications when the endometrium is artificially prepared for FET.
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引用次数: 0
Correlation of the umbilical cord coiling pattern and fetal outcome: A single-center observational analytical study
IF 3 2区 医学 Q2 DEVELOPMENTAL BIOLOGY Pub Date : 2025-02-20 DOI: 10.1016/j.placenta.2025.02.011
Diana Burlacu , Agnes Burlacu , Paul Călburean , Bela Szabo , Tibor Mezei

Introduction

The umbilical cord (UC) anatomically embodies the feto-placental bridge with a major role in fetal development due to the vascular structures embedded in Wharthon's jelly. The helical coiling of the umbilical cord may be counterclockwise, viewed from the fetus, defined as sinistral coiling, while the opposite as dextral coiling. This study aimed to determine any associations between UC coiling patterns and medical disorders of pregnancy.

Material and methods

An observational analytical study was conducted at the Clinical Emergency Hospital of Targu-Mures, Romania between January 2023–December 2023. Consecutive singleton placentas with attached UC submitted to the Pathology Department for various feto-maternal conditions were considered for appropriate measurements. The coiling number and direction (sinistral or dextral) of the umbilical cord were assessed per first 10 cm measured at the placental end.

Results

Of 187 cases this study included, 57.21 % (97) had sinistral and 42.79 % (90) had dextral UC coiling. The minimum and maximum maternal age group was 12–44 years old. Sinistral UC coiling was associated with an increased risk of spontaneous abortion and stillbirth (25.77 %, p = 0.028). Sinistral coiling was also associated with extreme prematurity (p = 0.013), smaller birth weight (p = 0.040) and lower placental weight (p = 0.029). A lower 1 min (p = 0.045) and 5 min Apgar score (p = 0.017) were associated with sinistral coiling. No relevant risk of premature rupture of membranes (PROM) was observed (p = 0.324). No significant association of sinistral coiling and metabolic or blood-related maternal diseases was observed (p = 0.385 and p = 0.725).

Conclusion

According to the literature approximately 25 % of all pregnancies have a dextral UC coiling direction. In contrast, in our study a significantly higher percentage was found (slightly higher than 42 %) to have dextral coiling of the UC. Data from our selected group indicated that certain neonatal pathologies (extreme prematurity, stillbirth, smaller birth weight, and lower Apgar score) were more associated with sinistral coiling as compared to dextral. More extensive studies are necessary to ascertain the clinical relevance of these data, particularly concerning high-risk pregnancies.
{"title":"Correlation of the umbilical cord coiling pattern and fetal outcome: A single-center observational analytical study","authors":"Diana Burlacu ,&nbsp;Agnes Burlacu ,&nbsp;Paul Călburean ,&nbsp;Bela Szabo ,&nbsp;Tibor Mezei","doi":"10.1016/j.placenta.2025.02.011","DOIUrl":"10.1016/j.placenta.2025.02.011","url":null,"abstract":"<div><h3>Introduction</h3><div>The umbilical cord (UC) anatomically embodies the feto-placental bridge with a major role in fetal development due to the vascular structures embedded in Wharthon's jelly. The helical coiling of the umbilical cord may be counterclockwise, viewed from the fetus, defined as sinistral coiling, while the opposite as dextral coiling. This study aimed to determine any associations between UC coiling patterns and medical disorders of pregnancy.</div></div><div><h3>Material and methods</h3><div>An observational analytical study was conducted at the Clinical Emergency Hospital of Targu-Mures, Romania between January 2023–December 2023. Consecutive singleton placentas with attached UC submitted to the Pathology Department for various feto-maternal conditions were considered for appropriate measurements. The coiling number and direction (sinistral or dextral) of the umbilical cord were assessed per first 10 cm measured at the placental end.</div></div><div><h3>Results</h3><div>Of 187 cases this study included, 57.21 % (97) had sinistral and 42.79 % (90) had dextral UC coiling. The minimum and maximum maternal age group was 12–44 years old. Sinistral UC coiling was associated with an increased risk of spontaneous abortion and stillbirth (25.77 %, p = 0.028). Sinistral coiling was also associated with extreme prematurity (p = 0.013), smaller birth weight (p = 0.040) and lower placental weight (p = 0.029). A lower 1 min (p = 0.045) and 5 min Apgar score (p = 0.017) were associated with sinistral coiling. No relevant risk of premature rupture of membranes (PROM) was observed (p = 0.324). No significant association of sinistral coiling and metabolic or blood-related maternal diseases was observed (p = 0.385 and p = 0.725).</div></div><div><h3>Conclusion</h3><div>According to the literature approximately 25 % of all pregnancies have a dextral UC coiling direction. In contrast, in our study a significantly higher percentage was found (slightly higher than 42 %) to have dextral coiling of the UC. Data from our selected group indicated that certain neonatal pathologies (extreme prematurity, stillbirth, smaller birth weight, and lower Apgar score) were more associated with sinistral coiling as compared to dextral. More extensive studies are necessary to ascertain the clinical relevance of these data, particularly concerning high-risk pregnancies.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"162 ","pages":"Pages 51-58"},"PeriodicalIF":3.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487218","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
Radiomics analysis of placental MRI for prenatal prediction of placenta accreta spectrum in pregnant women in the third trimester: A retrospective study of 594 patients
IF 3 2区 医学 Q2 DEVELOPMENTAL BIOLOGY Pub Date : 2025-02-19 DOI: 10.1016/j.placenta.2025.02.009
Kui Li , Guohui Yan , Xiaodan Zhang , Jianchun Kong , Yu Zou , Xiaodong Cheng

Objective

To develop and validate a model based on placental MRI for the prenatal prediction of placenta accreta spectrum (PAS) in pregnant women in the third trimester.

Materials and methods

A total of 594 pregnant women who were suspected of having PAS and underwent placental MRI antenatally were included and were allocated into the training cohort and testing cohort at a 2:1 ratio. MRI diagnosis was determined by three experienced radiologists. Radiomic features were extracted from images of T2 weighted imaging for each patient. After a feature selection strategy, a radiomics signature and a clinical-radiomics nomogram combining radiomics score and clinical risk factors were constructed to predict PAS. The performance of each model was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, and clinical utility.

Results

MRI diagnosis yielded AUCs of 0.77 and 0.79 for predicting PAS in the training and testing cohorts, respectively. The AUCs of the radiomics signature used to predict PAS in both cohorts were 0.80 and 0.83, respectively. The nomogram accurately predicted PAS in both cohorts (AUC = 0.84 and 0.89), with better results than those of MRI diagnosis and radiomics signature in the training (p = 0.009 and 0.003, respectively) and testing cohorts (p = 0.010 and 0.008, respectively), decision curve analysis confirmed its best clinical utility compared to the other models.

Conclusion

Radiomics analysis based on placental MRI may serve as an effective tool to predict PAS in patients with possible PAS in the third trimester.
{"title":"Radiomics analysis of placental MRI for prenatal prediction of placenta accreta spectrum in pregnant women in the third trimester: A retrospective study of 594 patients","authors":"Kui Li ,&nbsp;Guohui Yan ,&nbsp;Xiaodan Zhang ,&nbsp;Jianchun Kong ,&nbsp;Yu Zou ,&nbsp;Xiaodong Cheng","doi":"10.1016/j.placenta.2025.02.009","DOIUrl":"10.1016/j.placenta.2025.02.009","url":null,"abstract":"<div><h3>Objective</h3><div>To develop and validate a model based on placental MRI for the prenatal prediction of placenta accreta spectrum (PAS) in pregnant women in the third trimester.</div></div><div><h3>Materials and methods</h3><div>A total of 594 pregnant women who were suspected of having PAS and underwent placental MRI antenatally were included and were allocated into the training cohort and testing cohort at a 2:1 ratio. MRI diagnosis was determined by three experienced radiologists. Radiomic features were extracted from images of T2 weighted imaging for each patient. After a feature selection strategy, a radiomics signature and a clinical-radiomics nomogram combining radiomics score and clinical risk factors were constructed to predict PAS. The performance of each model was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, and clinical utility.</div></div><div><h3>Results</h3><div>MRI diagnosis yielded AUCs of 0.77 and 0.79 for predicting PAS in the training and testing cohorts, respectively. The AUCs of the radiomics signature used to predict PAS in both cohorts were 0.80 and 0.83, respectively. The nomogram accurately predicted PAS in both cohorts (AUC = 0.84 and 0.89), with better results than those of MRI diagnosis and radiomics signature in the training (<em>p</em> = 0.009 and 0.003, respectively) and testing cohorts (<em>p</em> = 0.010 and 0.008, respectively), decision curve analysis confirmed its best clinical utility compared to the other models.</div></div><div><h3>Conclusion</h3><div>Radiomics analysis based on placental MRI may serve as an effective tool to predict PAS in patients with possible PAS in the third trimester.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"162 ","pages":"Pages 59-66"},"PeriodicalIF":3.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511523","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
Amniotic fluid-derived exosomal miR-146a-5p ameliorates preeclampsia phenotypes by inhibiting HIF-1α/FLT-1 expression
IF 3 2区 医学 Q2 DEVELOPMENTAL BIOLOGY Pub Date : 2025-02-19 DOI: 10.1016/j.placenta.2025.02.013
Jin Lin , Xiaohong Huang , Jing Zhang , Weiming Yang , Fan Sun , Bo Huang , Wan Lu , Xiaozhong Wang

Introduction

Preeclampsia (PE) is a pregnancy-specific complication that begins with hypertension and proteinuria and seriously threatens the health of pregnant women and fetuses. Abnormal expression of amniotic fluid-derived exosomal miR-146a-5p was observed in PE. However, the role of human amniotic fluid-derived exosomes (AF-Exos) and miR-146a-5p in PE remains unclear.

Methods

We determined the miR-146a-5p expression pattern in the AF-Exos. AF-Exos, Cobalt chloride (CoCl2) and miR-146a-5p mimic were added to trophoblast cell lines HTR-8/SVneo and JEG-3, respectively. Then the proliferation and migration function of HTR-8/SVneo and JEG-3 cells were examined. The expression of miR-146a-5p, HIF-1α and FLT-1 in HTR-8/SVneo and JEG-3 cells were detected by RT-qPCR and western blotting. Finally, we determined the effect of AF-Exos in PE rat models.

Results

MiR-146a-5p was down-regulated in AF-Exos of PE compared to normal. Co-cultured with normal AF-Exos significantly promoted proliferation and migration of HTR-8/SVneo and JEG-3 cells. CoCl2 inhibited proliferation and migration of HTR-8/SVneo and JEG-3 cells, while miR-146a-5p mimic reversed them by suppressing HIF-1α/FLT-1 expression. After treatment of AF-Exos, the blood pressure and 24-h urinary protein of PE rats were substantially decreased, the quality of fetuses and placenta exhibited improved, and HIF-1α/FLT-1 expression of placenta, sFlt-1 and sEng levels of blood, were substantial suppressed.

Conclusion

The study provided experimental evidence for the protective effects of normal AF-Exos on ameliorating preeclampsia phenotypes, and miR-146a-5p may act an important role in enhancing the proliferation and migration of trophoblast cells by targeting HIF-1α.
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引用次数: 0
Difference in adverse neonatal outcomes between preterm singletons and twins possibly explained by placental abnormalities
IF 3 2区 医学 Q2 DEVELOPMENTAL BIOLOGY Pub Date : 2025-02-19 DOI: 10.1016/j.placenta.2025.02.010
Salma El Emrani , Jacqueline U.M. Termote , Esther J.S. Jansen , Jelle J. Goeman , Enrico Lopriore , Nicoline E. Schalij-Delfos , Lotte E. van der Meeren

Introduction

The purpose of this study was to compare microscopic placental characteristics between preterm twins and singletons, and between preterm monochorionic and dichorionic twins, in order to explore the effect of placental pathology on adverse neonatal outcomes.

Methods

This study included 566 neonates born ≤32 weeks and/or ≤1500 g, of whom 429 were singletons and 137 were twins (38 monochorionic and 99 dichorionic). Clinical data was retrospectively collected, and placentas were prospectively examined for maternal vascular malperfusion, fetal vascular malperfusion and placental inflammation (acute and chronic).

Results

Singletons had increased rates of maternal vascular malperfusion, fetal hypoxia, funisitis (in umbilical cord and chorial plate), chronic deciduitis, and villitis of unknown etiology compared to twins. Delayed villous maturation and ischemia were more frequently present in monochorionic placentas than in dichorionic. Singletons had a significant lower birthweight and were more often small for gestational age than twins. Multivariate linear regression analysis adjusting for singleton pregnancy, gestational hypertension and placental abnormalities showed that gestational hypertension (β = −114.8), infarct (β = −130.1), decidual necrosis (β = −115.4), fetal hypoxia (β = −59.3) and chronic deciduitis (β = −118.8) were independently associated with lower birthweight. Multivariate regression analysis revealed five independent risk factors of small for gestational age: gestational hypertension (OR 4.4), infarct (OR 3.7), decidual necrosis (OR 2.7), fetal hypoxia (OR 1.9) and villitis (OR 5.2).

Discussion

Singleton pregnancies vary in histological placental abnormality rates from twin pregnancies. This study demonstrated that differences in birthweight and small for gestational age rates between preterm twins and singletons can be attributed to gestational hypertension and histological placental abnormalities.
{"title":"Difference in adverse neonatal outcomes between preterm singletons and twins possibly explained by placental abnormalities","authors":"Salma El Emrani ,&nbsp;Jacqueline U.M. Termote ,&nbsp;Esther J.S. Jansen ,&nbsp;Jelle J. Goeman ,&nbsp;Enrico Lopriore ,&nbsp;Nicoline E. Schalij-Delfos ,&nbsp;Lotte E. van der Meeren","doi":"10.1016/j.placenta.2025.02.010","DOIUrl":"10.1016/j.placenta.2025.02.010","url":null,"abstract":"<div><h3>Introduction</h3><div>The purpose of this study was to compare microscopic placental characteristics between preterm twins and singletons, and between preterm monochorionic and dichorionic twins, in order to explore the effect of placental pathology on adverse neonatal outcomes.</div></div><div><h3>Methods</h3><div>This study included 566 neonates born ≤32 weeks and/or ≤1500 g, of whom 429 were singletons and 137 were twins (38 monochorionic and 99 dichorionic). Clinical data was retrospectively collected, and placentas were prospectively examined for maternal vascular malperfusion, fetal vascular malperfusion and placental inflammation (acute and chronic).</div></div><div><h3>Results</h3><div>Singletons had increased rates of maternal vascular malperfusion, fetal hypoxia, funisitis (in umbilical cord and chorial plate), chronic deciduitis, and villitis of unknown etiology compared to twins. Delayed villous maturation and ischemia were more frequently present in monochorionic placentas than in dichorionic. Singletons had a significant lower birthweight and were more often small for gestational age than twins. Multivariate linear regression analysis adjusting for singleton pregnancy, gestational hypertension and placental abnormalities showed that gestational hypertension (β = −114.8), infarct (β = −130.1), decidual necrosis (β = −115.4), fetal hypoxia (β = −59.3) and chronic deciduitis (β = −118.8) were independently associated with lower birthweight. Multivariate regression analysis revealed five independent risk factors of small for gestational age: gestational hypertension (OR 4.4), infarct (OR 3.7), decidual necrosis (OR 2.7), fetal hypoxia (OR 1.9) and villitis (OR 5.2).</div></div><div><h3>Discussion</h3><div>Singleton pregnancies vary in histological placental abnormality rates from twin pregnancies. This study demonstrated that differences in birthweight and small for gestational age rates between preterm twins and singletons can be attributed to gestational hypertension and histological placental abnormalities.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"162 ","pages":"Pages 45-50"},"PeriodicalIF":3.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Placental transcriptome analysis in opioid-exposed versus non-opioid exposed pregnancies
IF 3 2区 医学 Q2 DEVELOPMENTAL BIOLOGY Pub Date : 2025-02-17 DOI: 10.1016/j.placenta.2025.02.012
Aneya Sousa , Ojong Tabi Ojong Besong , Elisha M. Wachman , Elizabeth S. Taglauer , Jennifer E. Beane , Yohana Kefella , Ji Sun Koo , Kelley Saia , Hendree E. Jones , Huiping Zhang

Introduction

Opioid exposure during pregnancy may significantly alter gene expression in the placenta, potentially disrupting its function and influencing fetal brain development. These alterations may contribute to adverse outcomes such as neonatal opioid withdrawal syndrome (NOWS). In this study, we aim to systematically investigate the changes in placental gene expression associated with maternal opioid exposure to better understand the underlying molecular mechanisms and their implications for fetal health.

Methods

Fresh placental tissue samples were collected from 18 opioid-exposed pregnancies and 26 non-opioid-exposed control pregnancies. Transcriptomic changes related to opioid exposure were assessed using RNA sequencing (RNA-seq).

Results

Among the 16,172 genes detected, 55 showed differential expression (Padjusted < 0.25 or Punadjusted < 0.001) in opioid-exposed placentas. Gene Set Enrichment Analysis (GSEA) revealed that the differentially expressed genes were primarily associated with immune responses, neuronal development and function, as well as cell replication and division. Computational deconvolution using the PlacentaCellEnrich program identified significant enrichment of upregulated genes in decidual NK cells. Furthermore, integrative analysis of DNA methylation and gene expression showed an enrichment of differentially methylated genes among downregulated genes in opioid-exposed placentas.

Discussion

Our findings suggest that opioid exposure during pregnancy may disrupt critical placental pathways, particularly those involved in immune responses. Future studies focusing on transcriptomic changes in specific placental cell types will be essential for fully understanding the structural and functional alterations in the placenta due to opioid exposure during pregnancy.
{"title":"Placental transcriptome analysis in opioid-exposed versus non-opioid exposed pregnancies","authors":"Aneya Sousa ,&nbsp;Ojong Tabi Ojong Besong ,&nbsp;Elisha M. Wachman ,&nbsp;Elizabeth S. Taglauer ,&nbsp;Jennifer E. Beane ,&nbsp;Yohana Kefella ,&nbsp;Ji Sun Koo ,&nbsp;Kelley Saia ,&nbsp;Hendree E. Jones ,&nbsp;Huiping Zhang","doi":"10.1016/j.placenta.2025.02.012","DOIUrl":"10.1016/j.placenta.2025.02.012","url":null,"abstract":"<div><h3>Introduction</h3><div>Opioid exposure during pregnancy may significantly alter gene expression in the placenta, potentially disrupting its function and influencing fetal brain development. These alterations may contribute to adverse outcomes such as neonatal opioid withdrawal syndrome (NOWS). In this study, we aim to systematically investigate the changes in placental gene expression associated with maternal opioid exposure to better understand the underlying molecular mechanisms and their implications for fetal health.</div></div><div><h3>Methods</h3><div>Fresh placental tissue samples were collected from 18 opioid-exposed pregnancies and 26 non-opioid-exposed control pregnancies. Transcriptomic changes related to opioid exposure were assessed using RNA sequencing (RNA-seq).</div></div><div><h3>Results</h3><div>Among the 16,172 genes detected, 55 showed differential expression (<em>P</em><sub>adjusted</sub> &lt; 0.25 or <em>P</em><sub>unadjusted</sub> &lt; 0.001) in opioid-exposed placentas. Gene Set Enrichment Analysis (GSEA) revealed that the differentially expressed genes were primarily associated with immune responses, neuronal development and function, as well as cell replication and division. Computational deconvolution using the PlacentaCellEnrich program identified significant enrichment of upregulated genes in decidual NK cells. Furthermore, integrative analysis of DNA methylation and gene expression showed an enrichment of differentially methylated genes among downregulated genes in opioid-exposed placentas.</div></div><div><h3>Discussion</h3><div>Our findings suggest that opioid exposure during pregnancy may disrupt critical placental pathways, particularly those involved in immune responses. Future studies focusing on transcriptomic changes in specific placental cell types will be essential for fully understanding the structural and functional alterations in the placenta due to opioid exposure during pregnancy.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"162 ","pages":"Pages 27-34"},"PeriodicalIF":3.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445615","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
A retrospective analysis of placental histopathological findings in gestational diabetes mellitus (GDM)
IF 3 2区 医学 Q2 DEVELOPMENTAL BIOLOGY Pub Date : 2025-02-13 DOI: 10.1016/j.placenta.2025.02.008
Joseph Byrne , Niccole Ranaei-Zamani , J. Ciaran Hutchinson , Sara Hillman

Introduction

The placenta plays a pivotal role in supporting fetal growth and disruptions in its development and function can impact fetal outcomes. While placental pathology has been extensively studied in clinical conditions such as pre-eclampsia and fetal growth restriction (FGR), the association between placental abnormalities and gestational diabetes mellitus (GDM) is still unclear. This study aims to explore the placental pathology associated with GDM, shedding light on potential links to adverse perinatal outcomes.

Methods

A retrospective cohort study was conducted using electronic patient data from the Fetal Medicine and Neonatal Units at University College London Hospital. Placental samples were obtained and analysed at Great Ormond Street Hospital. Maternal demographics, obstetric history and placental histopathology were reviewed. Statistical analyses were performed to identify associations and risk factors.

Results

Of the 2580 pregnancies analysed, 341 were GDM pregnancies, 549 had FGR and 66 had both GDM and FGR. GDM pregnancies required increased rates of obstetric intervention and neonatal care admission. Placental pathology in GDM revealed a higher prevalence of maternal vascular malperfusion (MVM) lesions, whilst GDM-related FGR showed further associations with MVM lesions and adverse perinatal outcomes.

Discussion

Our study highlights MVM lesions as a prominent feature in the placentas of GDM pregnancies, especially when associated with FGR. These lesions are linked to adverse perinatal outcomes, emphasizing the need for enhanced antenatal care in these cases. The study contributes insights into the complex relationship between GDM, placental pathology and adverse fetal outcomes, laying the foundation for future investigations into early interventional strategies.
导言胎盘在支持胎儿生长方面起着关键作用,其发育和功能的紊乱会影响胎儿的预后。虽然胎盘病理学已在子痫前期和胎儿生长受限(FGR)等临床病症中得到广泛研究,但胎盘异常与妊娠期糖尿病(GDM)之间的关系仍不清楚。本研究旨在探讨与 GDM 相关的胎盘病理学,揭示其与不良围产期结局的潜在联系。方法:本研究利用伦敦大学学院医院胎儿医学和新生儿科的电子患者数据进行了一项回顾性队列研究。胎盘样本在大奥蒙德街医院采集并分析。对产妇的人口统计学特征、产科病史和胎盘组织病理学进行了审查。结果 在分析的 2580 例妊娠中,341 例为 GDM 妊娠,549 例为 FGR 妊娠,66 例同时患有 GDM 和 FGR。GDM 孕妇需要产科干预和新生儿护理的比例增加。GDM 胎盘病理学显示母体血管灌注不良(MVM)病变的发生率较高,而 GDM 相关的 FGR 显示 MVM 病变与不良围产期结局有进一步的关联。这些病变与不良围产期结局有关,强调了对这些病例加强产前保健的必要性。该研究有助于深入了解 GDM、胎盘病变和胎儿不良结局之间的复杂关系,为今后研究早期干预策略奠定基础。
{"title":"A retrospective analysis of placental histopathological findings in gestational diabetes mellitus (GDM)","authors":"Joseph Byrne ,&nbsp;Niccole Ranaei-Zamani ,&nbsp;J. Ciaran Hutchinson ,&nbsp;Sara Hillman","doi":"10.1016/j.placenta.2025.02.008","DOIUrl":"10.1016/j.placenta.2025.02.008","url":null,"abstract":"<div><h3>Introduction</h3><div>The placenta plays a pivotal role in supporting fetal growth and disruptions in its development and function can impact fetal outcomes. While placental pathology has been extensively studied in clinical conditions such as pre-eclampsia and fetal growth restriction (FGR), the association between placental abnormalities and gestational diabetes mellitus (GDM) is still unclear. This study aims to explore the placental pathology associated with GDM, shedding light on potential links to adverse perinatal outcomes.</div></div><div><h3>Methods</h3><div>A retrospective cohort study was conducted using electronic patient data from the Fetal Medicine and Neonatal Units at University College London Hospital. Placental samples were obtained and analysed at Great Ormond Street Hospital. Maternal demographics, obstetric history and placental histopathology were reviewed. Statistical analyses were performed to identify associations and risk factors.</div></div><div><h3>Results</h3><div>Of the 2580 pregnancies analysed, 341 were GDM pregnancies, 549 had FGR and 66 had both GDM and FGR. GDM pregnancies required increased rates of obstetric intervention and neonatal care admission. Placental pathology in GDM revealed a higher prevalence of maternal vascular malperfusion (MVM) lesions, whilst GDM-related FGR showed further associations with MVM lesions and adverse perinatal outcomes.</div></div><div><h3>Discussion</h3><div>Our study highlights MVM lesions as a prominent feature in the placentas of GDM pregnancies, especially when associated with FGR. These lesions are linked to adverse perinatal outcomes, emphasizing the need for enhanced antenatal care in these cases. The study contributes insights into the complex relationship between GDM, placental pathology and adverse fetal outcomes, laying the foundation for future investigations into early interventional strategies.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"162 ","pages":"Pages 20-26"},"PeriodicalIF":3.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419969","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
Research design and tissue collection considerations for investigation of placenta accreta spectrum.
IF 3 2区 医学 Q2 DEVELOPMENTAL BIOLOGY Pub Date : 2025-02-11 DOI: 10.1016/j.placenta.2025.02.006
Stacy Zamudio, Nicholas P Illsley

Placenta accreta spectrum (PAS) is a group of pregnancy pathologies characterized by loss/absence of decidua and trophoblast over-invasion penetrating into the myometrium beyond the normal depth. It is associated with expansion of deeper branches of the uterine arteries and placental adherence to the uterus. Undetected PAS leads frequently to massive and potentially fatal hemorrhage at delivery. For the more severe forms of PAS (increta, percreta), the most frequent solution is caesarean delivery-hysterectomy. The etiology of PAS is, however, unclear at best. While there is increasing research interest, the clinical intricacies of this pathology pose significant challenges for the researcher. In this communication we present the elements which we believe should be considered when undertaking (or interpreting) research into PAS, particularly when biological samples and molecular techniques are involved.

{"title":"Research design and tissue collection considerations for investigation of placenta accreta spectrum.","authors":"Stacy Zamudio, Nicholas P Illsley","doi":"10.1016/j.placenta.2025.02.006","DOIUrl":"https://doi.org/10.1016/j.placenta.2025.02.006","url":null,"abstract":"<p><p>Placenta accreta spectrum (PAS) is a group of pregnancy pathologies characterized by loss/absence of decidua and trophoblast over-invasion penetrating into the myometrium beyond the normal depth. It is associated with expansion of deeper branches of the uterine arteries and placental adherence to the uterus. Undetected PAS leads frequently to massive and potentially fatal hemorrhage at delivery. For the more severe forms of PAS (increta, percreta), the most frequent solution is caesarean delivery-hysterectomy. The etiology of PAS is, however, unclear at best. While there is increasing research interest, the clinical intricacies of this pathology pose significant challenges for the researcher. In this communication we present the elements which we believe should be considered when undertaking (or interpreting) research into PAS, particularly when biological samples and molecular techniques are involved.</p>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433637","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
Stillbirth at term in Iceland: Causes of death and patterns of placental injury
IF 3 2区 医学 Q2 DEVELOPMENTAL BIOLOGY Pub Date : 2025-02-11 DOI: 10.1016/j.placenta.2025.02.007
Ragnheidur I. Bjarnadottir , Thora Steffensen , Karin Pettersson , Nikos Papadogiannakis , Alexander K. Smarason , Johanna Gunnarsdottir

Background

Iceland is a high-income country with <400.000 inhabitants and low stillbirth rate (SBR). Increased antenatal risk assessment and interventions in high-risk pregnancies doubled the induction rate after 2008.

Objective

Estimate the SBR at term, comparing an earlier (1996–2008) and latter (2009–2021) 13-year period, and describe causes of death and patterns of placental injury of infants stillborn at term.

Study design

Stillbirth at term was defined as antepartum or intrapartum death of an infant that was diagnosed after ≥37 weeks of gestation. All cases (n = 125) had placental examination. Histopathological slides were reviewed, and pattern of placental injury classified according to the Amsterdam consensus. Medical records were found for all mothers who had stillbirth at term and cause of death assigned according to the Stockholm classification of stillbirth.

Results

No decrease in the SBR at term was found between periods. Majority of deaths (72 %) were caused by cord complications and/or placental insufficiency and deaths attributed to placental insufficiency increased in the latter period. Placentas weighing under the 10th percentile were more common in the latter period, 43.5 % vs. 30.2 % (p < 0.05) as was chronic villitis of unknown etiology (VUE), 40.3 % vs. 12.7 % (p < 0.01).

Conclusion

Stillbirth at term has not decreased in Iceland, despite increased antenatal surveillance and induction rate, with more deaths attributed to placental insufficiency and VUE increasingly found in the later period. Further research is needed on the correlation of patterns of placental injury with clinical phenotypes of mothers and infants.
{"title":"Stillbirth at term in Iceland: Causes of death and patterns of placental injury","authors":"Ragnheidur I. Bjarnadottir ,&nbsp;Thora Steffensen ,&nbsp;Karin Pettersson ,&nbsp;Nikos Papadogiannakis ,&nbsp;Alexander K. Smarason ,&nbsp;Johanna Gunnarsdottir","doi":"10.1016/j.placenta.2025.02.007","DOIUrl":"10.1016/j.placenta.2025.02.007","url":null,"abstract":"<div><h3>Background</h3><div>Iceland is a high-income country with &lt;400.000 inhabitants and low stillbirth rate (SBR). Increased antenatal risk assessment and interventions in high-risk pregnancies doubled the induction rate after 2008.</div></div><div><h3>Objective</h3><div>Estimate the SBR at term, comparing an earlier (1996–2008) and latter (2009–2021) 13-year period, and describe causes of death and patterns of placental injury of infants stillborn at term.</div></div><div><h3>Study design</h3><div>Stillbirth at term was defined as antepartum or intrapartum death of an infant that was diagnosed after ≥37 weeks of gestation. All cases (n = 125) had placental examination. Histopathological slides were reviewed, and pattern of placental injury classified according to the Amsterdam consensus. Medical records were found for all mothers who had stillbirth at term and cause of death assigned according to the Stockholm classification of stillbirth.</div></div><div><h3>Results</h3><div>No decrease in the SBR at term was found between periods. Majority of deaths (72 %) were caused by cord complications and/or placental insufficiency and deaths attributed to placental insufficiency increased in the latter period. Placentas weighing under the 10th percentile were more common in the latter period, 43.5 % vs. 30.2 % (p &lt; 0.05) as was chronic villitis of unknown etiology (VUE), 40.3 % vs. 12.7 % (p &lt; 0.01).</div></div><div><h3>Conclusion</h3><div>Stillbirth at term has not decreased in Iceland, despite increased antenatal surveillance and induction rate, with more deaths attributed to placental insufficiency and VUE increasingly found in the later period. Further research is needed on the correlation of patterns of placental injury with clinical phenotypes of mothers and infants.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"162 ","pages":"Pages 14-19"},"PeriodicalIF":3.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Placenta
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