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Annual Review of Cell and Developmental... 2015The placenta sits at the interface between the maternal and fetal vascular beds where it mediates nutrient and waste exchange to enable in utero existence. Placental... (Review)
Review
The placenta sits at the interface between the maternal and fetal vascular beds where it mediates nutrient and waste exchange to enable in utero existence. Placental cells (trophoblasts) accomplish this via invading and remodeling the uterine vasculature. Amazingly, despite being of fetal origin, trophoblasts do not trigger a significant maternal immune response. Additionally, they maintain a highly reliable hemostasis in this extremely vascular interface. Decades of research into how the placenta differentiates itself from embryonic tissues to accomplish these and other feats have revealed a previously unappreciated level of complexity with respect to the placenta's cellular composition. Additionally, novel insights with respect to roles played by the placenta in guiding fetal development and metabolism have sparked a renewed interest in understanding the interrelationship between fetal and placental well-being. Here, we present an overview of emerging research in placental biology that highlights these themes and the importance of the placenta to fetal and adult health.
Topics: Animals; Biological Transport; Female; Fetal Development; Humans; Placenta; Pregnancy; Trophoblasts
PubMed: 26443191
DOI: 10.1146/annurev-cellbio-100814-125620 -
Placenta Jul 2020The placenta is essential for the efficient delivery of nutrients and oxygen from mother to fetus to maintain normal fetal growth. Dysfunctional placental development... (Review)
Review
The placenta is essential for the efficient delivery of nutrients and oxygen from mother to fetus to maintain normal fetal growth. Dysfunctional placental development underpins many pregnancy complications, including fetal growth restriction (FGR) a condition in which the fetus does not reach its growth potential. The FGR placenta is smaller than normal placentae throughout gestation and displays maldevelopment of both the placental villi and the fetal vasculature within these villi. Specialized epithelial cells called trophoblasts exhibit abnormal function and development in FGR placentae. This includes an altered balance between proliferation and apoptotic death, premature cellular senescence, and reduced colonisation of the maternal decidual tissue. Thus, the placenta undergoes aberrant changes at the macroscopic to cellular level in FGR, which can limit exchange capacity and downstream fetal growth. This review aims to compile stereological, in vitro, and imaging data to create a holistic overview of the FGR placenta and its pathophysiology, with a focus on the contribution of trophoblasts.
Topics: Animals; Chorionic Villi; Female; Fetal Growth Retardation; Humans; Infant, Newborn; Infant, Small for Gestational Age; Placenta; Placentation; Pregnancy; Trophoblasts
PubMed: 32421528
DOI: 10.1016/j.placenta.2020.05.003 -
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 -
Nature Protocols Oct 2020The human placenta is essential for successful reproduction. There is great variation in the anatomy and development of the placenta in different species, meaning that...
The human placenta is essential for successful reproduction. There is great variation in the anatomy and development of the placenta in different species, meaning that animal models provide limited information about human placental development and function. Until recently, it has been impossible to isolate trophoblast cells from the human placenta that proliferate in vitro. This has limited our ability to understand pregnancy disorders. Generating an in vitro model that recapitulates the unique features of the human placenta has been challenging. The first in vitro model system of human trophoblast that could be cultured long term and differentiated to syncytiotrophoblast (SCT) and extravillous trophoblast (EVT) was a two-dimensional (2D) culture system of human trophoblast stem cells. Here, we describe a protocol to isolate trophoblast from first-trimester human placentas that can be grown long term in a three-dimensional (3D) organoid culture system. Trophoblast organoids can be established within 2-3 weeks, passaged every 7-10 d, and cultured for over a year. The structural organization of these human trophoblast organoids closely resembles the villous placenta with a layer of cytotrophoblast (VCT) that differentiates into superimposed SCT. Altering the composition of the medium leads to differentiation of the trophoblast organoids into HLA-G+ EVT cells which rapidly migrate and invade through the Matrigel droplet in which they are cultured. Our previous research confirmed that there is similarity between the trophoblast organoids and in vivo placentas in their transcriptomes and ability to produce placental hormones. This organoid culture system provides an experimental model to investigate human placental development and function as well as interactions of trophoblast cells with the local and systemic maternal environment.
Topics: Cell Culture Techniques; Cell Differentiation; Female; Humans; Organoids; Placenta; Pregnancy; Stem Cells; Trophoblasts
PubMed: 32908314
DOI: 10.1038/s41596-020-0381-x -
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 -
Advances in Anatomy, Embryology, and... 2021This chapter focuses on the early stages of placental development in horses and their relatives in the genus Equus and highlights unique features of equid reproductive...
This chapter focuses on the early stages of placental development in horses and their relatives in the genus Equus and highlights unique features of equid reproductive biology. The equine placenta is classified as a noninvasive, epitheliochorial type. However, equids have evolved a minor component of invasive trophoblast, the chorionic girdle and endometrial cups, which links the equine placenta with the highly invasive hemochorial placentae of rodents and, particularly, with the primate placenta. Two types of fetus-to-mother signaling in equine pregnancy are mediated by the invasive equine trophoblast cells. First, endocrinological signaling mediated by equine chorionic gonadotrophin (eCG) drives maternal progesterone production to support the equine conceptus between days 40 and 100 of gestation. Only in primates and equids does the placenta produce a gonadotrophin, but the evolutionary paths taken by these two groups of mammals to produce this placental signal were very different. Second, florid expression of paternal major histocompatibility complex (MHC) class I molecules by invading chorionic girdle cells stimulates strong maternal anti-fetal antibody responses that may play a role in the development of immunological tolerance that protects the conceptus from destruction by the maternal immune system. In humans, invasive extravillous trophoblasts also express MHC class I molecules, but the loci involved, and their likely function, are different from those of the horse. Comparison of the cellular and molecular events in these disparate species provides outstanding examples of convergent evolution and co-option in mammalian pregnancy and highlights how studies of the equine placenta have produced new insights into reproductive strategies.
Topics: Animals; Chorion; Endometrium; Female; Horses; Placenta; Placentation; Pregnancy; Trophoblasts
PubMed: 34694479
DOI: 10.1007/978-3-030-77360-1_6 -
Annals of Biomedical Engineering Aug 2021Research into the human placenta's complex functioning is complicated by a lack of suitable physiological in vivo models. Two complementary approaches have emerged... (Review)
Review
Research into the human placenta's complex functioning is complicated by a lack of suitable physiological in vivo models. Two complementary approaches have emerged recently to address these gaps in understanding, computational in silico techniques, including multi-scale modeling of placental blood flow and oxygen transport, and cellular in vitro approaches, including organoids, tissue engineering, and organ-on-a-chip models. Following a brief introduction to the placenta's structure and function and its influence on the substantial clinical problem of preterm birth, these different bioengineering approaches are reviewed. The cellular techniques allow for investigation of early first-trimester implantation and placental development, including critical biological processes such as trophoblast invasion and trophoblast fusion, that are otherwise very difficult to study. Similarly, computational models of the placenta and the pregnant pelvis at later-term gestation allow for investigations relevant to complications that occur when the placenta has fully developed. To fully understand clinical conditions associated with the placenta, including those with roots in early processes but that only manifest clinically at full-term, a holistic approach to the study of this fascinating, temporary but critical organ is required.
Topics: Female; Humans; Models, Biological; Placenta; Pregnancy; Tissue Engineering
PubMed: 33420547
DOI: 10.1007/s10439-020-02714-7 -
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 -
American Journal of Reproductive... Jul 2016Nearly 65 years have passed since Peter Medawar posed the following question: "How does the pregnant mother contrive to nourish within itself, for many weeks or months,... (Review)
Review
Nearly 65 years have passed since Peter Medawar posed the following question: "How does the pregnant mother contrive to nourish within itself, for many weeks or months, a fetus that is an antigenically foreign body." Now, understanding of reproductive immunology has demonstrated that the HLA antigens in the placenta are non-classical and do not induce rejection. In the placenta and in tumors, 50% or more of the cells are cells of the immune system and were once thought to be primed and ready for killing tumors or the "fetal transplant" but these cells are not potential killers but abet the growth of either the tumor or the placenta. We believe that these cells are there to create an environment, which enhances either placental or tumor growth. By examining the similarities of the placenta's and tumor's immune cells, novel mechanisms to cause tumors to be eliminated can be devised.
Topics: Animals; Female; Humans; Maternal-Fetal Exchange; Models, Immunological; Neoplasms; Placenta; Pregnancy
PubMed: 27293114
DOI: 10.1111/aji.12524 -
Advances in Experimental Medicine and... 2023The placenta is an intriguing organ that allows us to survive intrauterine life. This essential organ connects both mother and fetus and plays a crucial role in maternal... (Review)
Review
The placenta is an intriguing organ that allows us to survive intrauterine life. This essential organ connects both mother and fetus and plays a crucial role in maternal and fetal well-being. This chapter presents an overview of the morphological and functional aspects of human placental development. First, we describe early human placental development and the characterization of the cell types found in the human placenta. Second, the human placenta from the second trimester to the term of gestation is reviewed, focusing on the morphology and specific pathologies that affect the placenta. Finally, we focus on the placenta's primary functions, such as oxygen and nutrient transport, and their importance for placental development.
Topics: Pregnancy; Female; Humans; Placenta; Fetus; Placentation; Fetal Development
PubMed: 37466767
DOI: 10.1007/978-3-031-32554-0_1