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Nature Nov 2018During early human pregnancy the uterine mucosa transforms into the decidua, into which the fetal placenta implants and where placental trophoblast cells intermingle and...
During early human pregnancy the uterine mucosa transforms into the decidua, into which the fetal placenta implants and where placental trophoblast cells intermingle and communicate with maternal cells. Trophoblast-decidual interactions underlie common diseases of pregnancy, including pre-eclampsia and stillbirth. Here we profile the transcriptomes of about 70,000 single cells from first-trimester placentas with matched maternal blood and decidual cells. The cellular composition of human decidua reveals subsets of perivascular and stromal cells that are located in distinct decidual layers. There are three major subsets of decidual natural killer cells that have distinctive immunomodulatory and chemokine profiles. We develop a repository of ligand-receptor complexes and a statistical tool to predict the cell-type specificity of cell-cell communication via these molecular interactions. Our data identify many regulatory interactions that prevent harmful innate or adaptive immune responses in this environment. Our single-cell atlas of the maternal-fetal interface reveals the cellular organization of the decidua and placenta, and the interactions that are critical for placentation and reproductive success.
Topics: Cell Communication; Cell Differentiation; Decidua; Female; Fetus; Histocompatibility, Maternal-Fetal; Humans; Killer Cells, Natural; Ligands; Placenta; Pregnancy; RNA, Small Cytoplasmic; Sequence Analysis, RNA; Single-Cell Analysis; Stromal Cells; Transcriptome; Trophoblasts
PubMed: 30429548
DOI: 10.1038/s41586-018-0698-6 -
Environment International Jan 2021Microplastics are particles smaller than five millimeters deriving from the degradation of plastic objects present in the environment. Microplastics can move from the... (Review)
Review
Microplastics are particles smaller than five millimeters deriving from the degradation of plastic objects present in the environment. Microplastics can move from the environment to living organisms, including mammals. In this study, six human placentas, collected from consenting women with physiological pregnancies, were analyzed by Raman Microspectroscopy to evaluate the presence of microplastics. In total, 12 microplastic fragments (ranging from 5 to 10 μm in size), with spheric or irregular shape were found in 4 placentas (5 in the fetal side, 4 in the maternal side and 3 in the chorioamniotic membranes); all microplastics particles were characterized in terms of morphology and chemical composition. All of them were pigmented; three were identified as stained polypropylene a thermoplastic polymer, while for the other nine it was possible to identify only the pigments, which were all used for man-made coatings, paints, adhesives, plasters, finger paints, polymers and cosmetics and personal care products.
Topics: Animals; Environmental Monitoring; Female; Humans; Microplastics; Placenta; Plastics; Pregnancy; Water Pollutants, Chemical
PubMed: 33395930
DOI: 10.1016/j.envint.2020.106274 -
Human Reproduction Update Jun 2020In humans, inadequate trophoblast invasion into the decidua is associated with the 'great obstetrical syndromes' which include pre-eclampsia, foetal growth restriction... (Review)
Review
BACKGROUND
In humans, inadequate trophoblast invasion into the decidua is associated with the 'great obstetrical syndromes' which include pre-eclampsia, foetal growth restriction (FGR) and stillbirth. The mechanisms regulating invasion remain poorly understood, although interactions with the uterine environment are clearly of central importance. Extravillous trophoblast (EVT) cells invade the uterus and transform the spiral arteries. Progress in understanding how they invade has been limited due to the lack of good in vitro models. Firstly, there are no non-malignant cell lines that have an EVT phenotype. Secondly, the invasion assays used are of limited use for the small numbers of primary EVT available from first-trimester placentas. We discuss recent progress in this field with the generation of new EVT lines and invasion assays using microfluidic technology.
OBJECTIVE AND RATIONALE
Our aim is to describe the established models used to study human trophoblast invasion in vivo and in vitro. The difficulties of obtaining primary cells and cell lines that recapitulate the phenotype of EVT are discussed together with the advantages and pitfalls of the different invasion assays. We compare these traditional end point assays to microfluidic assays where the dynamics of migration can be measured.
SEARCH METHODS
Relevant studies were identified by PubMed search, last updated on February 2020. A search was conducted to determine the number of journal articles published using the cell lines JEG-3, BeWo, JAR, HTR-8/Svneo, Swan-71 and primary human extravillous trophoblast in the last 5 years.
OUTCOMES
Deep trophoblast invasion into the maternal decidua is a particular feature of human pregnancy. This invasion needs to be finely regulated to allocate resources between mother and baby. A reliable source of EVT is needed to study in vitro how the uterine environment regulates this process. First, we critically discuss the issues with the trophoblast cell lines currently used; for example, most of them lack expression of the defining marker of EVT, HLA-G. Recently, advances in human stem cell and organoid technology have been applied to extraembryonic tissues to develop trophoblast cell lines that can grow in two (2D) and three dimensions (3D) and differentiate to EVT. This means that the 'trophoblast' cell lines currently in use should rapidly become obsolete. Second, we critically discuss the problems with assays to study trophoblast invasion. These lack physiological relevance and have simplified migration dynamics. Microfluidic assays are a powerful tool to study cell invasion because they require only a few cells, which are embedded in 3D in an extracellular matrix. Their major advantage is real-time monitoring of cell movement, enabling detailed analysis of the dynamics of trophoblast migration.
WIDER IMPLICATIONS
Trophoblast invasion in the first trimester of pregnancy remains poorly understood despite the importance of this process in the pathogenesis of pre-eclampsia, FGR, stillbirth and recurrent miscarriage. The new technologies described here will allow investigation into this critical process.
Topics: Abortion, Habitual; Cell Culture Techniques; Cell Line; Cell Movement; Embryo Implantation; Female; Humans; Models, Biological; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, First; Trophoblasts
PubMed: 32441309
DOI: 10.1093/humupd/dmaa017 -
Proceedings of the National Academy of... Sep 2017The human placenta is a dynamic and heterogeneous organ critical in the establishment of the fetomaternal interface and the maintenance of gestational well-being. It is...
The human placenta is a dynamic and heterogeneous organ critical in the establishment of the fetomaternal interface and the maintenance of gestational well-being. It is also the major source of cell-free fetal nucleic acids in the maternal circulation. Placental dysfunction contributes to significant complications, such as preeclampsia, a potentially lethal hypertensive disorder during pregnancy. Previous studies have identified significant changes in the expression profiles of preeclamptic placentas using whole-tissue analysis. Moreover, studies have shown increased levels of targeted RNA transcripts, overall and placental contributions in maternal cell-free nucleic acids during pregnancy progression and gestational complications, but it remains infeasible to noninvasively delineate placental cellular dynamics and dysfunction at the cellular level using maternal cell-free nucleic acid analysis. In this study, we addressed this issue by first dissecting the cellular heterogeneity of the human placenta and defined individual cell-type-specific gene signatures by analyzing more than 24,000 nonmarker selected cells from full-term and early preeclamptic placentas using large-scale microfluidic single-cell transcriptomic technology. Our dataset identified diverse cellular subtypes in the human placenta and enabled reconstruction of the trophoblast differentiation trajectory. Through integrative analysis with maternal plasma cell-free RNA, we resolved the longitudinal cellular dynamics of hematopoietic and placental cells in pregnancy progression. Furthermore, we were able to noninvasively uncover the cellular dysfunction of extravillous trophoblasts in early preeclamptic placentas. Our work showed the potential of integrating transcriptomic information derived from single cells into the interpretation of cell-free plasma RNA, enabling the noninvasive elucidation of cellular dynamics in complex pathological conditions.
Topics: Cell-Free Nucleic Acids; Female; Humans; Microfluidic Analytical Techniques; Placenta; Plasma; Pre-Eclampsia; Pregnancy; RNA; Single-Cell Analysis; Transcriptome; Trophoblasts
PubMed: 28830992
DOI: 10.1073/pnas.1710470114 -
Cells Dec 2022The placenta is an important organ for fetal and maternal health during pregnancy and impacts offspring health late in life. Defects in placental vasculature and...
BACKGROUND
The placenta is an important organ for fetal and maternal health during pregnancy and impacts offspring health late in life. Defects in placental vasculature and trophoblast have been identified in several pregnancy complications. Thus, the detailed molecular profile and heterogeneity of endothelial cells and trophoblasts in placentas will aid us in better understanding placental behaviors and improving pregnancy outcomes.
METHODS
Single-cell RNA sequencing (scRNA-seq) was performed to profile the transcriptomics of human placental villous tissues from eleven patients with normal pregnancies in the first and second trimesters (6-16 weeks of gestation).
RESULTS
The transcriptomic landscape of 52,179 single cells was obtained, and the cells were classified as trophoblasts, fibroblasts, endothelial cells, erythroid cells, Hofbauer cells, and macrophages. Our analysis further revealed the three subtypes of placental endothelial cells, with distinct metabolic signatures and transcription factor regulatory networks. We also determined the transcriptomic features of the trophoblast subpopulations and characterized two distinct populations of progenitor cells in cytotrophoblasts, which were capable of differentiating to extravillous trophoblasts and syncytiotrophoblasts, respectively.
CONCLUSIONS
Our study provided a high-resolution molecular profile of the human placenta between 6 and 16 weeks of gestation. Our data revealed the placental cell complexity and demonstrated the transcriptional networks and signaling involved in placental endothelial and trophoblast differentiation during early pregnancy, which will be a resource for future studies of the human placental development.
Topics: Humans; Pregnancy; Female; Placenta; Trophoblasts; Endothelial Cells; Placentation; Cell Differentiation; Sequence Analysis, RNA
PubMed: 36611882
DOI: 10.3390/cells12010087 -
Molecules and Cells May 2022Trophoblasts, important functional cells in the placenta, play a critical role in maintaining placental function. The heterogeneity of trophoblasts has been reported,...
Trophoblasts, important functional cells in the placenta, play a critical role in maintaining placental function. The heterogeneity of trophoblasts has been reported, but little is known about the trophoblast subtypes and distinctive functions during preeclampsia (PE). In this study, we aimed to gain insight into the cell type-specific transcriptomic changes by performing unbiased single-cell RNA sequencing (scRNA-seq) of placental tissue samples, including those of patients diagnosed with PE and matched healthy controls. A total of 29,006 cells were identified in 11 cell types, including trophoblasts and immune cells, and the functions of the trophoblast subtypes in the PE group and the control group were also analyzed. As an important trophoblast subtype, extravillous trophoblasts (EVTs) were further divided into 4 subgroups, and their functions were preliminarily analyzed. We found that some biological processes related to pregnancy, hormone secretion and immunity changed in the PE group. We also identified and analyzed the regulatory network of transcription factors (TFs) identified in the EVTs, among which 3 modules were decreased in the PE group. Then, through cell experiments, we found that in one of the modules, CEBPB and GTF2B may be involved in EVT dysfunction in PE. In conclusion, our study showed the different transcriptional profiles and regulatory modules in trophoblasts between placentas in the control and PE groups at the single-cell level; these changes may be involved in the pathological process of PE, providing a new molecular theoretical basis for preeclamptic trophoblast dysfunction.
Topics: Cell Movement; Female; Humans; Placenta; Pre-Eclampsia; Pregnancy; Sequence Analysis, RNA; Transcriptome; Trophoblasts
PubMed: 35289305
DOI: 10.14348/molcells.2021.0211 -
ELife Aug 2022Infections at the maternal-fetal interface can directly harm the fetus and induce complications that adversely impact pregnancy outcomes. Innate immune signaling by both...
Infections at the maternal-fetal interface can directly harm the fetus and induce complications that adversely impact pregnancy outcomes. Innate immune signaling by both fetal-derived placental trophoblasts and the maternal decidua must provide antimicrobial defenses at this critical interface without compromising its integrity. Here, we developed matched trophoblast (TO) and decidua organoids (DO) from human placentas to define the relative contributions of these cells to antiviral defenses at the maternal-fetal interface. We demonstrate that TO and DO basally secrete distinct immunomodulatory factors, including the constitutive release of the antiviral type III interferon IFN-λ2 from TOs, and differentially respond to viral infections through the induction of organoid-specific factors. Finally, we define the differential susceptibility and innate immune signaling of TO and DO to human cytomegalovirus (HCMV) and develop a co-culture model of TO and DO which showed that trophoblast-derived factors protect decidual cells from HCMV infection. Our findings establish matched TO and DO as ex vivo models to study vertically transmitted infections and highlight differences in innate immune signaling by fetal-derived trophoblasts and the maternal decidua.
Topics: Antiviral Agents; Decidua; Female; Humans; Immunity, Innate; Organoids; Placenta; Pregnancy; Trophoblasts
PubMed: 35975985
DOI: 10.7554/eLife.79794 -
International Journal of Molecular... Apr 2024We are pleased to present this Special Issue of the , entitled "Physiology and Pathophysiology of Placenta 2 [...].
We are pleased to present this Special Issue of the , entitled "Physiology and Pathophysiology of Placenta 2 [...].
Topics: Humans; Placenta; Pregnancy; Female; Animals; Placenta Diseases
PubMed: 38731805
DOI: 10.3390/ijms25094586 -
Reproduction (Cambridge, England) Nov 2016The very apt definition of a placenta is coined by Mossman, namely apposition or fusion of the fetal membranes to the uterine mucosa for physiological exchange. As such,... (Review)
Review
The very apt definition of a placenta is coined by Mossman, namely apposition or fusion of the fetal membranes to the uterine mucosa for physiological exchange. As such, it is a specialized organ whose purpose is to provide continuing support to the developing young. By this definition, placentas have evolved within every vertebrate class other than birds. They have evolved on multiple occasions, often within quite narrow taxonomic groups. As the placenta and the maternal system associate more intimately, such that the conceptus relies extensively on maternal support, the relationship leads to increased conflict that drives adaptive changes on both sides. The story of vertebrate placentation, therefore, is one of convergent evolution at both the macromolecular and molecular levels. In this short review, we first describe the emergence of placental-like structures in nonmammalian vertebrates and then transition to mammals themselves. We close the review by discussing the mechanisms that might have favored diversity and hence evolution of the morphology and physiology of the placentas of eutherian mammals.
Topics: Animals; Biological Evolution; Female; Humans; Placenta; Placentation; Pregnancy
PubMed: 27486265
DOI: 10.1530/REP-16-0325 -
Frontiers in Immunology 2024Melatonin (N-acetyl-5-methoxytryptamine) is an indolamine hormone with many physiological and biological roles. Melatonin is an antioxidant, anti-inflammatory, free... (Review)
Review
Melatonin (N-acetyl-5-methoxytryptamine) is an indolamine hormone with many physiological and biological roles. Melatonin is an antioxidant, anti-inflammatory, free radical scavenger, circadian rhythm regulator, and sleep hormone. However, its most popular role is the ability to regulate sleep through the circadian rhythm. Interestingly, recent studies have shown that melatonin is an important and essential hormone during pregnancy, specifically in the placenta. This is primarily due to the placenta's ability to synthesize its own melatonin rather than depending on the pineal gland. During pregnancy, melatonin acts as an antioxidant and anti-inflammatory, which is necessary to ensure a stable environment for both the mother and the fetus. It is an essential antioxidant in the placenta because it reduces oxidative stress by constantly scavenging for free radicals, i.e., maintain the placenta's integrity. In a healthy pregnancy, the maternal immune system is constantly altered to accommodate the needs of the growing fetus, and melatonin acts as a key anti-inflammatory by regulating immune homeostasis during early and late gestation. This literature review aims to identify and summarize melatonin's role as a powerful antioxidant and anti-inflammatory that reduces oxidative stress and inflammation to maintain a favorable homeostatic environment in the placenta throughout gestation.
Topics: Pregnancy; Female; Humans; Melatonin; Antioxidants; Placenta; Free Radical Scavengers; Anti-Inflammatory Agents
PubMed: 38361952
DOI: 10.3389/fimmu.2024.1339304