PlacentaPub Date : 2024-11-01DOI: 10.1016/j.placenta.2024.03.007
S.C. Glättli , F.A. Elzinga , W. van der Bijl , H.G.D. Leuvenink , J.R. Prins , H. van Goor , S.J. Gordijn , P. Olinga , D.J. Touw , P. Mian
{"title":"Variability in perfusion conditions and set-up parameters used in ex vivo human placenta models: A literature review","authors":"S.C. Glättli , F.A. Elzinga , W. van der Bijl , H.G.D. Leuvenink , J.R. Prins , H. van Goor , S.J. Gordijn , P. Olinga , D.J. Touw , P. Mian","doi":"10.1016/j.placenta.2024.03.007","DOIUrl":"10.1016/j.placenta.2024.03.007","url":null,"abstract":"<div><div>The <em>ex vivo</em> human placenta perfusion model has proven to be clinically relevant to study transfer- and fetal exposure of various drugs. Although the method has existed for a long period, the setup of the perfusion model has not been generalized yet. This review aims to summarize the setups of <em>ex vivo</em> placental perfusion models used to examine drug transfer across the placenta to identify generalized properties and differences across setups. A literature search was carried out in PubMed September 26, 2022. Studies were labeled as relevant when information was reported, between 2000 and 2022, on the setups of <em>ex vivo</em> placental perfusion models used to study drug transfer across the placenta. The placenta perfusion process, and the data extraction, was divided into phases of <em>preparation, control, drug,</em> and <em>experimental</em> reflecting the chronological timeline of the different phases during the entire placental perfusion process. 135 studies describing an <em>ex vivo</em> human placental perfusion experiment were included. Among included studies, the majority (78.5%) analyzed drug perfusion in maternal to fetal direction, 18% evaluated bi-directional drug perfusion, 3% under equilibrium conditions, and one study investigated drug perfusion in fetal to maternal direction. This literature review facilitates the comparison of studies that employ similar placenta perfusion protocols for drug transfer studies and reveals significant disparities in the setup of these <em>ex vivo</em> placental perfusion models. Due to interlaboratory variability, perfusion studies are not readily comparable or interchangeable. Therefore, a stepwise protocol with multiple checkpoints for validating placental perfusion is needed.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"157 ","pages":"Pages 37-49"},"PeriodicalIF":3.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140270120","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}
PlacentaPub Date : 2024-11-01DOI: 10.1016/j.placenta.2024.06.010
Padma Murthi , Bill Kalionis
{"title":"Homeobox genes in the human placenta: Twists and turns on the path to find novel targets","authors":"Padma Murthi , Bill Kalionis","doi":"10.1016/j.placenta.2024.06.010","DOIUrl":"10.1016/j.placenta.2024.06.010","url":null,"abstract":"<div><div>Fetal growth restriction (FGR) is a clinically important human pregnancy disorder that is thought to originate early in pregnancy and while its aetiology is not well understood, the disorder is associated with placental insufficiency. Currently treatment for FGR is limited by increased surveillance using ultrasound monitoring and premature delivery, or corticosteroid medication in the third trimester to prolong pregnancy. There is a pressing need for novel strategies to detect and treat FGR at its early stage. Homeobox genes are well established as master regulators of early embryonic development and increasing evidence suggests they are also important in regulating early placental development. Most important is that specific homeobox genes are abnormally expressed in human FGR. This review focusses on identifying the molecular pathways controlled by homeobox genes in the normal and FGR-affected placenta. This information will begin to address the knowledge gap in the molecular aetiology of FGR and lay the foundation for identifying potential diagnostic and therapeutic targets.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"157 ","pages":"Pages 28-36"},"PeriodicalIF":3.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440792","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}
PlacentaPub Date : 2024-11-01DOI: 10.1016/j.placenta.2024.02.006
Prabu Karthick Parameshwar , Cathy Vaillancourt , Christopher Moraes
{"title":"Engineering placental trophoblast fusion: A potential role for biomechanics in syncytialization","authors":"Prabu Karthick Parameshwar , Cathy Vaillancourt , Christopher Moraes","doi":"10.1016/j.placenta.2024.02.006","DOIUrl":"10.1016/j.placenta.2024.02.006","url":null,"abstract":"<div><div><span>The process by which placental trophoblasts fuse to form the syncytiotrophoblast<span> around the chorionic villi is not fully understood. Mechanical features of the </span></span><em>in vivo</em> and <em>in vitro</em> culture environments have recently emerged as having the potential to influence fusion efficiency, and considering these mechanical cues may ultimately allow predictive control of trophoblast syncytialization. Here, we review recent studies that suggest that biomechanical factors such as shear stress, tissue stiffness, and dimensionally-related stresses affect villous trophoblast fusion efficiency. We then discuss how these stimuli might arise <em>in vivo</em><span> and how they can be incorporated in cultures to study and enhance villous trophoblast fusion. We believe that this mechanical paradigm will provide novel insight into manipulating the syncytialization process to better engineer improved models, understand disease progression, and ultimately develop novel therapeutic strategies.</span></div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"157 ","pages":"Pages 50-54"},"PeriodicalIF":3.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139919151","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}
PlacentaPub Date : 2024-11-01DOI: 10.1016/j.placenta.2024.02.007
Gregory E. Rice , Carlos Salomon
{"title":"IFPA Joan Hunt Senior Award in Placentology lecture: Extracellular vesicle signalling and pregnancy","authors":"Gregory E. Rice , Carlos Salomon","doi":"10.1016/j.placenta.2024.02.007","DOIUrl":"10.1016/j.placenta.2024.02.007","url":null,"abstract":"<div><div>The field of extracellular vesicle (EV) signalling has the potential to transform our understanding of maternal-fetal communication and affords new opportunities for non-invasive prenatal testing and therapeutic intervention. EVs have been implicated in implantation, placentation<span><span><span>, maternal adaptation to pregnancy and complications of pregnancy, being detectable in maternal circulation as early as 6 weeks of pregnancy. EVs of differing biogenic origin, composition and </span>bioactivity are released by cells to maintain </span>homoeostasis<span>. Induction of EV signalling is associated with aberrant cellular metabolism and manifests as changes in EV concentrations and/or composition. Characterizing such changes affords opportunity to develop more informative diagnostics and efficacious interventions. To develop accurate and reliable EV-based diagnostics requires: identification of disease-associated biomarkers in specific EV subpopulations; and rapid, reproducible and scalable sample processing. Conventional isolation methods face challenges due to co-isolation of particles with similar physicochemical properties. Methods targeting specific vesicle-surface epitopes and compatible with automated platforms show promise. Effective EV therapeutics require precise targeting, achieved through genetic<span><span> engineering to release EVs expressing cell-targeting ligands and carrying therapeutic payloads. Unlike cell-based therapies, this approach offers advantages including: low immunogenicity; stability; and long-term storage. Although EV diagnostics and therapeutics in </span>reproductive biology are nascent, available technologies can enhance our understanding of EV signalling between mother and fetus, its role in pregnancies and improve outcomes.</span></span></span></div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"157 ","pages":"Pages 5-13"},"PeriodicalIF":3.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140008970","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}
PlacentaPub Date : 2024-11-01DOI: 10.1016/j.placenta.2024.09.016
Samantha G. Zambuto , Samyuktha S. Kolluru , Brendan A.C. Harley , Michelle L. Oyen
{"title":"Gelatin methacryloyl biomaterials and strategies for trophoblast research","authors":"Samantha G. Zambuto , Samyuktha S. Kolluru , Brendan A.C. Harley , Michelle L. Oyen","doi":"10.1016/j.placenta.2024.09.016","DOIUrl":"10.1016/j.placenta.2024.09.016","url":null,"abstract":"<div><div>Rising maternal mortality rates in the U.S. are a significant public health issue that must be addressed; however, much of the basic science information required to target pregnancy-related pathologies have not yet been defined. Placental and blastocyst implantation research are challenging to perform in humans because of the early time frame of these processes in pregnancy and limited access to first trimester tissues. As a result, there is a critical need to develop model systems capable of studying these processes in increasing mechanistic detail. With the recent passing of the FDA Modernization Act 2.0 and advances in tissue engineering methods, three-dimensional microphysiological model systems offer an exciting opportunity to model early stages of placentation. Here, we detail the synthesis, characterization, and application of gelatin methacryloyl (GelMA) hydrogel platforms for studying trophoblast behavior in three-dimensional hydrogel systems. Photopolymerization strategies to fabricate GelMA hydrogels render the hydrogels homogeneous in terms of structure and stable under physiological temperatures, allowing for rigorous fabrication of reproducible hydrogel variants. Unlike other natural polymers that have minimal opportunity to tune their properties, GelMA hydrogel properties can be tuned across many axes of variation, including polymer degree of functionalization, gelatin bloom strength, light exposure time and intensity, polymer weight percent, photoinitiator concentration, and physical geometry. In this work, we aim to inspire and instruct the field to utilize GelMA biomaterial strategies for future placental research. With enhanced microphysiological models of pregnancy, we can now generate the basic science information required to address problems in pregnancy.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"157 ","pages":"Pages 67-75"},"PeriodicalIF":3.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352521","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}
PlacentaPub Date : 2024-11-01DOI: 10.1016/j.placenta.2024.09.004
Larry Chamley
{"title":"Trophoblast Research Editorial 27th International Federation of Placenta Associations Conference, Rotorua, New Zealand","authors":"Larry Chamley","doi":"10.1016/j.placenta.2024.09.004","DOIUrl":"10.1016/j.placenta.2024.09.004","url":null,"abstract":"","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"157 ","pages":"Page 1"},"PeriodicalIF":3.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257787","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}
PlacentaPub Date : 2024-11-01DOI: 10.1016/j.placenta.2023.11.004
Sathish Kumar , Ruolin Song , Jay S. Mishra
{"title":"Elevated gestational testosterone impacts vascular and uteroplacental function","authors":"Sathish Kumar , Ruolin Song , Jay S. Mishra","doi":"10.1016/j.placenta.2023.11.004","DOIUrl":"10.1016/j.placenta.2023.11.004","url":null,"abstract":"<div><div><span><span>Maternal vascular adaptations to establish an adequate blood supply<span><span> to the uterus and placenta<span> are essential for optimal nutrient and oxygen delivery to the developing fetus in eutherian mammals, including humans. Numerous factors contribute to maintaining appropriate hemodynamics and placental vascular development throughout pregnancy. Failure to achieve or sustain these pregnancy-associated changes in women is strongly associated with an increased risk of antenatal complications, such as </span></span>preeclampsia<span>, a hypertensive disorder of pregnancy. The precise etiology of preeclampsia is unknown, but emerging evidence points to a potential role for androgens. The association between androgens and maternal cardiovascular and </span></span></span>placental function merits particular attention due to the notable 2- to 3-fold elevated </span>plasma testosterone<span><span> (T) levels observed in preeclampsia. T levels in preeclamptic women positively correlate with vascular dysfunction, and preeclampsia is associated with increased androgen receptor<span><span><span> (AR) levels in placental tissues. Moreover, animal studies replicating the pattern and magnitude of T increase observed in preeclamptic pregnancies have reproduced key features of preeclampsia, including gestational hypertension, </span>endothelial dysfunction, heightened </span>vasoconstriction<span> to angiotensin II<span><span>, impaired spiral artery remodeling, placental </span>hypoxia, reduced nutrient transport, and </span></span></span></span>fetal growth restriction. Collectively, these findings suggest that AR-mediated activity plays a significant role in the clinical presentation of preeclampsia. This review critically evaluates this hypothesis, considering both clinical and preclinical evidence.</span></div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"157 ","pages":"Pages 14-20"},"PeriodicalIF":3.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135669966","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}
PlacentaPub Date : 2024-11-01DOI: 10.1016/j.placenta.2024.09.014
Jess C. Hercus , Daniel Alejandro Salcedo Rubio , Maria Elisa Osorio Nieto , Mackenzie M.L. Sturn , Cheayeong Keum , Julian K. Christians
{"title":"The whole is lesser than the sum of its parts? Dissecting layer-enriched samples of rodent placenta is worth the effort","authors":"Jess C. Hercus , Daniel Alejandro Salcedo Rubio , Maria Elisa Osorio Nieto , Mackenzie M.L. Sturn , Cheayeong Keum , Julian K. Christians","doi":"10.1016/j.placenta.2024.09.014","DOIUrl":"10.1016/j.placenta.2024.09.014","url":null,"abstract":"<div><div>Gene expression in the placenta, assessed by bulk RNA-seq, is a common method to explore placental function. Many rodent studies homogenize the entire placenta, and yet doing so may obscure differences within specific functional regions such as the labyrinth, junctional zone and decidua. Conversely, analysis of the whole placenta could generate apparent differences due to changes in composition (e.g., relative amounts of labyrinth vs junctional zone) rather than differential gene expression. We assess the value of dissecting and separately analysing the labyrinth and junctional zone/decidua by comparing RNA-seq results from the labyrinth, junctional zone/decidua combined, and whole placenta from an experiment examining effects of maternal food restriction and fetal sex in C57BL6/J mice at gestational day 17.5. The number of genes identified as differentially expressed in response to maternal food restriction was substantially higher in the labyrinth (910 genes), than in the junctional zone/decidua (50 genes), which in turn was slightly higher than in the whole placenta (3 genes). Only one gene was differentially expressed in all 3 tissue types, and 20 genes were differentially expressed in both the labyrinth and junctional zone/decidua. The larger number of differentially expressed genes in the labyrinth was due to both larger effect sizes and estimates of effect sizes having smaller standard errors. While dissection to obtain layer-enriched samples is slightly more time-consuming than collection of whole placenta and requires some practice, our results show that layer-enrichment is clearly worth the effort.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"157 ","pages":"Pages 76-80"},"PeriodicalIF":3.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352522","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}
PlacentaPub Date : 2024-11-01DOI: 10.1016/j.placenta.2024.08.011
D. Mark , J.L. James
{"title":"Preeclampsia - A patient's perspective","authors":"D. Mark , J.L. James","doi":"10.1016/j.placenta.2024.08.011","DOIUrl":"10.1016/j.placenta.2024.08.011","url":null,"abstract":"<div><div>The opening session of the 2023 International Federation of Placenta Associations meeting included a powerful patient perspective from invited guest Dawn Mark about her experience with preeclampsia and stillbirth. As part of this issue of Trophoblast Research we invited Dawn to provide this in written form, to more widely share her important message. Her children's names have been changed to protect privacy.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"157 ","pages":"Pages 2-4"},"PeriodicalIF":3.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257789","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}
PlacentaPub Date : 2024-11-01DOI: 10.1016/j.placenta.2024.06.009
William R. Cooke, Gabriel Davis Jones, Christopher WG. Redman, Manu Vatish
{"title":"Small RNAs in the pathogenesis of preeclampsia","authors":"William R. Cooke, Gabriel Davis Jones, Christopher WG. Redman, Manu Vatish","doi":"10.1016/j.placenta.2024.06.009","DOIUrl":"10.1016/j.placenta.2024.06.009","url":null,"abstract":"<div><div>Preeclampsia is a major contributor to maternal and fetal morbidity and mortality. The disorder can be classified into early- and late-onset subtypes, both of which evolve in two stages. The first stage comprises the development of pre-clinical, utero-placental malperfusion. Early and late utero-placental malperfusion have different causes and time courses. Early-onset preeclampsia (20 % of cases) is driven by dysfunctional placentation in the first half of pregnancy. In late-onset preeclampsia (80 % of cases), malperfusion is a consequence of placental compression within the confines of a limited uterine cavity. In both subtypes, the malperfused placenta releases stress signals into the maternal circulation. These stress signals trigger onset of the clinical syndrome (the second stage). Small RNA molecules, which are implicated in cellular stress responses in general, may be involved at different stages. Micro RNAs contribute to abnormal trophoblast invasion, immune dysregulation, angiogenic imbalance, and syncytiotrophoblast-derived extracellular vesicle signalling in preeclampsia. Transfer RNA fragments are placental signals known to be specifically involved in cell stress responses. Disorder-specific differences in small nucleolar RNAs and piwi-interacting RNAs have also been reported. Here, we summarise key small RNA advances in preeclampsia pathogenesis. We propose that existing small RNA classifications are unhelpful and that non-biased assessment of RNA expression, incorporation of non-annotated molecules and consideration of chemical modifications to RNAs may be important in elucidating preeclampsia pathogenesis.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"157 ","pages":"Pages 21-27"},"PeriodicalIF":3.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141493102","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}