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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 -
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 -
Seminars in Reproductive Medicine 2000Despite the critical role the placenta plays in governing the outcome of pregnancy, a great deal remains to be learned about this transient organ. Several factors have... (Review)
Review
Despite the critical role the placenta plays in governing the outcome of pregnancy, a great deal remains to be learned about this transient organ. Several factors have contributed to our relative lack of knowledge. For example, most of the placenta's development, which precedes that of the embryo or fetus, occurs during the first half of pregnancy in humans. Thus, it is difficult to obtain the tissue samples that are required to study relevant time points. In addition, placental anatomy is complex; one of the most interesting parts can be obtained only by biopsy of the uterine wall. Recent analyses of these biopsies, combined with information from cell culture models, revealed the unexpected finding that placental cells that invade the uterus phenocopy many endothelial cell characteristics. This finding has several interesting implications for normal pregnancy and for pregnancy complications that could be related, either directly or indirectly, to this phenomenon, such as preeclampsia and cytomegalovirus transmission.
Topics: Cytomegalovirus Infections; Embryonic and Fetal Development; Female; Humans; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Trophoblasts
PubMed: 11299970
DOI: 10.1055/s-2000-12569 -
Cells, Tissues, Organs 2016The placenta is a temporal, dynamic and diverse organ with important immunological features that facilitate embryonic and fetal development and survival, notwithstanding... (Review)
Review
The placenta is a temporal, dynamic and diverse organ with important immunological features that facilitate embryonic and fetal development and survival, notwithstanding the fact that several aspects of its formation and function closely resemble tumor progression. Placentation in mammals is commonly used to characterize the evolution of species, including insights into human evolution. Although most placentas are discarded after birth, they are a high-yield source for the isolation of stem/progenitor cells and are rich in extracellular matrix (ECM), representing an important resource for regenerative medicine purposes. Interactions among cells, ECM and bioactive molecules regulate tissue and organ generation and comprise the foundation of tissue engineering. In the present article, differences among several mammalian species regarding the placental types and classifications, phenotypes and potency of placenta-derived stem/progenitor cells, placental ECM components and current placental ECM applications were reviewed to highlight their potential clinical and biomedical relevance.
Topics: Animals; Cell Differentiation; Extracellular Matrix; Female; Humans; Placenta; Placentation; Pregnancy; Regenerative Medicine; Stem Cells; Tissue Engineering
PubMed: 27050810
DOI: 10.1159/000443636 -
Journal of Reproductive Immunology Dec 2010Feto-maternal immune transfer occurs via both the placenta in utero and colostrum after birth. The layers between the maternal and fetal circulation systems, known as... (Review)
Review
Feto-maternal immune transfer occurs via both the placenta in utero and colostrum after birth. The layers between the maternal and fetal circulation systems, known as the placental barrier, regulate immune transfer to the fetus via the placenta. The placental barrier, as well as the type of placental structure, is species specific. The extent of transfer of antibodies from mother to fetus is related to the number of placental barrier layers. Passive immunity via the colostrum is essential in species in which the type of placentation impedes contact between maternal and fetal circulation systems, hindering the transfer of antibodies. In these species, susceptibility to neonatal infections is increased if colostrum is not ingested. Acquired antibodies are of extreme importance for adaptation of the neonate to the extrauterine environment. Based on the aforementioned factors, it was observed that in synepitheliochorial and epitheliochorial placentas immune transfer via the placenta is not possible, except in cases of placental alteration (e.g., placentitis). On the other hand, the mechanism of transfer in endothelial and hemochorial placentas is facilitated compared with other placentas. We conclude that there are no appreciable qualitative differences between the two mechanisms of transfer (placenta and colostrum) and that immune protection in the neonate can be attained by either mechanism.
Topics: Animals; Colostrum; Female; Fetus; Humans; Immunity, Maternally-Acquired; Placenta; Placental Circulation; Placentation; Pregnancy
PubMed: 20956021
DOI: 10.1016/j.jri.2010.08.062 -
Critical Reviews in Clinical Laboratory... Mar 2019The cynomolgus monkey is increasingly considered in toxicological research as the most appropriate model for humans due to the species' close physiological contiguity,... (Review)
Review
The cynomolgus monkey is increasingly considered in toxicological research as the most appropriate model for humans due to the species' close physiological contiguity, including reproductive physiology. Here, literature on the cynomolgus monkey placenta is reviewed in regards to its similarity to the human placenta and particularly for its immunological role, which is not entirely mirrored in humans. Pertinent original data are included in this article. The cynomolgus monkey placenta is evaluated based on three aspects: first, morphological development; second, the spatial and temporal appearance of maternal and fetal immune cells and certain immune cell products of the innate and adaptive immune systems; and third, the expression of relevant immune tolerance-related molecules including the homologs of anti-human leucocyte antigen, indoleamine 2,3-dioxygenase, FAS/FAS-L, annexin II, and progesterone. Parameters relevant to the immunological role of the placenta are evaluated from the immunologically immature stage of gestational day (GD) 50 until more mature stages close to birth. Selected comparisons are drawn with human and other laboratory animal placentas. In conclusion, the cynomolgus monkey placenta has a high degree of morphological and physiological similarity to the human placenta. However, there are differences in the topographical distribution of cell types and immune tolerance-related molecules. Three basic features are recognized: (1) the immunological capacity of the placenta changes throughout the lifetime of the organ; (2) these immunological changes include multiple parameters such as morphological adaptations, cell type involvement, and changes in immune-relevant molecule expression; and (3) the immune systems of two genetically disparate individuals (mother and child) are functionally intertwined at the maternal-fetal interface.
Topics: Animals; Female; Humans; Macaca fascicularis; Placenta; Pregnancy
PubMed: 30632863
DOI: 10.1080/10408363.2018.1538200 -
Toxicologic Pathology 2014This short review is derived from the peer-reviewed literature and the experience and case materials of the authors. Brief illustrated summaries are presented on the... (Review)
Review
This short review is derived from the peer-reviewed literature and the experience and case materials of the authors. Brief illustrated summaries are presented on the gross and histologic normal anatomy of rodent and macaque placentas, including typical organ weights, with comments on differences from the human placenta. Common incidental findings, background lesions, and induced toxic lesions are addressed, and a recommended strategy for pathologic evaluation of placentas is provided.
Topics: Animals; Female; Histocytochemistry; Humans; Pathology; Placenta; Pregnancy; Toxicology
PubMed: 23531795
DOI: 10.1177/0192623313482207 -
Biochemical Society Transactions Feb 2000The human haemochorial placenta is a complex and dynamic interface between embryonic and maternal tissues. A myriad array of compounds has been identified at this... (Review)
Review
The human haemochorial placenta is a complex and dynamic interface between embryonic and maternal tissues. A myriad array of compounds has been identified at this interface, some of which exert local effects which might be important in maintaining the integrity of the organ. These compounds are diverse in nature and function; they include enzymes, hormones and bioactive peptides. Successful nidation requires the synchronization of endometrial maturation and embryonic development. The complex nature of this interface requires the application of sound sampling strategies. The new stereological methods have thrown fresh light on the growth and development of the human placenta. These methods permit the objective, quantitative description of morphology by efficient design-based methods. This approach has permitted a better definition of the functional morphology of the placenta. Applications of these methodologies are providing a spatial and temporal framework on which to lay the new physiological and molecular information. Here we review the essential features of the stereological approach, identify useful structural quantities and provide some examples of their application. The problems associated with the quantification of immunocytochemistry are illustrated with the use of immunoreactivity to insulin-like growth factor I receptor in normal placentae and in pre-eclampsia. Although stereology can provide useful quantitative information about the structure of this dynamic tissue, other anatomical methods that could be applied to better define the relationships between structure and function will be discussed. These include confocal microscopy, to examine the dynamic physiological interactions of the different tissue compartments, and low-temperature electron microscopy techniques such as cryosubstitution, to allow better access to the biochemical information resident in the tissue. The complex and dynamic nature of the tissue requires a multidisciplinary approach; central to these investigations is a comprehensive understanding of its fine structure.
Topics: Estradiol; Humans; Immunohistochemistry; Membranes; Microscopy, Confocal; Placenta
PubMed: 10816128
DOI: 10.1042/bst0280202 -
Toxicologic Pathology 2014This review summarizes the potential and also some limitations of using human placentas, or placental cells and structures for toxicology testing. The placenta contains... (Review)
Review
This review summarizes the potential and also some limitations of using human placentas, or placental cells and structures for toxicology testing. The placenta contains a wide spectrum of cell types and tissues, such as trophoblast cells, immune cells, fibroblasts, stem cells, endothelial cells, vessels, glands, membranes, and many others. It may be expected that in many cases the relevance of results obtained from human placenta will be higher than those from animal models due to species specificity of metabolism and placental structure. For practical and economical reasons, we propose to apply a battery of sequential experiments for analysis of potential toxicants. This should start with using cell lines, followed by testing placenta tissue explants and isolated placenta cells, and finally by application of single and dual side ex vivo placenta perfusion. With each of these steps, the relative workload increases while the number of feasible repeats decreases. Simultaneously, the predictive power enhances by increasing similarity with in vivo human conditions. Toxic effects may be detected by performing proliferation, vitality and cell death assays, analysis of protein and hormone expression, immunohistochemistry or testing functionality of signaling pathways, gene expression, transport mechanisms, and so on. When toxic effects appear at any step, the subsequent assays may be cancelled. Such a system may be useful to reduce costs and increase specificity in testing questionable toxicants. Nonetheless, it requires further standardization and end point definitions for better comparability of results from different toxicants and to estimate the respective in vivo translatability and predictive value.
Topics: Female; Humans; Placenta; Pregnancy; Toxicity Tests
PubMed: 23548605
DOI: 10.1177/0192623313482206