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Placenta Sep 2018The most important function of the placenta is the exchange of nutrients and oxygen between a mother and her fetus. To establish a healthy functioning placenta,... (Review)
Review
The most important function of the placenta is the exchange of nutrients and oxygen between a mother and her fetus. To establish a healthy functioning placenta, placentation needs to occur with adequate remodelling of spiral arteries by extravillous trophoblasts. When this process is impaired, the resulting suboptimal and inadequate placenta function results in the manifestation of pregnancy complications. Impaired placenta function can cause preeclampsia and leads to fetal growth restriction due to hypoxia. Presence of hypoxia leads to oxidative stress due to an imbalance between reactive oxygen species and antioxidants, thereby causing damage to proteins, lipids and DNA. In the placenta, signs of morphological adaptation in response to hypoxia can be found. Different placental lesions like maternal or fetal vascular malperfusion or chronic villitis lead to a decreased exchange of oxygen between the mother and the fetus. Clinically, several biomarkers indicative for oxidative stress, e.g. malondialdehyde and reduced levels of free thiols are found. This review aims to give an overview of the causes and (potential) role of placental oxidative stress in the development of placental parenchymal pathology and its clinical consequences. Also, therapeutic options aiming at prevention or treatment of hypoxia of the placenta and fetus are described.
Topics: Female; Humans; Oxidative Stress; Placenta; Placenta Diseases; Placentation; Pregnancy; Reactive Oxygen Species
PubMed: 29622278
DOI: 10.1016/j.placenta.2018.03.003 -
Journal of Human Hypertension Aug 2023Higher blood pressure prior to pregnancy is associated with increased risk of placental abruption, hypertension and preeclampsia, preterm delivery and fetal growth... (Review)
Review
Higher blood pressure prior to pregnancy is associated with increased risk of placental abruption, hypertension and preeclampsia, preterm delivery and fetal growth restriction. These conditions are jointly termed placental syndromes as they are characterised by impaired placentation and early placental vascularization. Placental syndromes are associated with an increased maternal risk of progression to hypertension and cardiovascular disease (CVD) in later life. Women affected by both a clinical placental syndrome and with evidence of placental maternal vascular malperfusion (MVM) have a particularly high risk of hypertension and CVD. Yet whether placental impairment and clinical syndromes are causes or consequences of higher blood pressure in women remains unclear. In this review, we address the relationship between blood pressure and maternal health in pregnancy. We conclude that there is a pressing need for studies with a range of detailed measures of cardiac and vascular structure and function taken before, during and after pregnancy to solve the 'chicken and egg' puzzle of women's blood pressure and pregnancy health, and to inform effective precision medicine prevention and treatment of both placental syndromes and chronic hypertension in women.
Topics: Pregnancy; Female; Humans; Placenta; Syndrome; Hypertension; Pre-Eclampsia; Cardiovascular Diseases; Placentation
PubMed: 36702879
DOI: 10.1038/s41371-023-00802-4 -
American Journal of Reproductive... Sep 2019The maternal-fetal interface represents a unique immune privileged site that maintains the ability to defend against pathogens while orchestrating the necessary tissue... (Review)
Review
The maternal-fetal interface represents a unique immune privileged site that maintains the ability to defend against pathogens while orchestrating the necessary tissue remodeling required for placentation. The recent discovery of novel cellular families (innate lymphoid cells, tissue-resident NK cells) suggests that our understanding of the decidual immunome is incomplete. To understand this complex milieu, new technological developments allow reproductive immunologists to collect increasingly complex data at a cellular resolution. Polychromatic flow cytometry allows for greater resolution in the identification of novel cell types by surface and intracellular protein. Single-cell RNA-seq coupled with microfluidics allows for efficient cellular transcriptomics. The extreme dimensionality and size of data sets generated, however, requires the application of novel computational approaches for unbiased analysis. There are now multiple dimensionality reduction (tSNE, SPADE) and visualization tools (SPICE) that allow researchers to efficiently analyze flow cytometry data. Development of computational tools has also been extended to RNA-seq data (including scRNA-seq), which requires specific analytical tools. Here, we provide an overview and a brief primer for the reproductive immunology community on data acquisition and computational tools for the analysis of complex flow cytometry and RNA-seq data.
Topics: Decidua; Female; Flow Cytometry; Gene Expression Profiling; Humans; Placentation; Pregnancy; RNA-Seq; Reproductive Medicine; Single-Cell Analysis
PubMed: 31206899
DOI: 10.1111/aji.13157 -
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 -
Proceedings of the National Academy of... Jan 2023Establishment of the hemochorial uterine-placental interface requires exodus of trophoblast cells from the placenta and their transformative actions on the uterus, which...
Establishment of the hemochorial uterine-placental interface requires exodus of trophoblast cells from the placenta and their transformative actions on the uterus, which represent processes critical for a successful pregnancy, but are poorly understood. We examined the involvement of CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxyl-terminal domain 2 (CITED2) in rat and human trophoblast cell development. The rat and human exhibit deep hemochorial placentation. CITED2 was distinctively expressed in the junctional zone (JZ) and invasive trophoblast cells of the rat. Homozygous gene deletion resulted in placental and fetal growth restriction. Small null placentas were characterized by disruptions in the JZ, delays in intrauterine trophoblast cell invasion, and compromised plasticity. In the human placentation site, CITED2 was uniquely expressed in the extravillous trophoblast (EVT) cell column and importantly contributed to the development of the EVT cell lineage. We conclude that CITED2 is a conserved regulator of deep hemochorial placentation.
Topics: Animals; Female; Humans; Pregnancy; Rats; Placenta; Placentation; Repressor Proteins; Trans-Activators; Trophoblasts; Uterus
PubMed: 36626551
DOI: 10.1073/pnas.2213622120 -
Biomolecules Oct 2023Endogenous retroviruses (ERVs) are retrovirus-like sequences that were previously integrated into the host genome. Although most ERVs are inactivated by mutations,... (Review)
Review
Endogenous retroviruses (ERVs) are retrovirus-like sequences that were previously integrated into the host genome. Although most ERVs are inactivated by mutations, deletions, or epigenetic regulation, some remain transcriptionally active and impact host physiology. Several ERV-encoded proteins, such as Syncytins and Suppressyn, contribute to placenta acquisition, a crucial adaptation in mammals that protects the fetus from external threats and other risks while enabling the maternal supply of oxygen, nutrients, and antibodies. In primates, Syncytin-1 and Syncytin-2 facilitate cell-cell fusion for placental formation. Suppressyn is the first ERV-derived protein that inhibits cell fusion by binding to ASCT2, the receptor for Syncytin-1. Furthermore, Syncytin-2 likely inserted into the genome of the common ancestor of Anthropoidea, whereas Syncytin-1 and Suppressyn likely inserted into the ancestor of catarrhines; however, they were inactivated in some lineages, suggesting that multiple exaptation events had occurred. This review discusses the role of ERV-encoded proteins, particularly Syncytins and Suppressyn, in placental development and function, focusing on the integration of ERVs into the host genome and their contribution to the genetic mechanisms underlying placentogenesis. This review provides valuable insights into the molecular and genetic aspects of placentation, potentially shedding light on broader evolutionary and physiological processes in mammals.
Topics: Animals; Pregnancy; Female; Placenta; Endogenous Retroviruses; Epigenesis, Genetic; Placentation; Gene Products, env; Mammals
PubMed: 37892164
DOI: 10.3390/biom13101482 -
International Journal of Molecular... Jul 2022In humans, the placenta provides the only fetomaternal connection and is essential for establishing a pregnancy as well as fetal well-being. Additionally, it allows... (Review)
Review
In humans, the placenta provides the only fetomaternal connection and is essential for establishing a pregnancy as well as fetal well-being. Additionally, it allows maternal physiological adaptation and embryonic immunological acceptance, support, and nutrition. The placenta is derived from extra-embryonic tissues that develop rapidly and dynamically in the first weeks of pregnancy. It is primarily composed of trophoblasts that differentiate into villi, stromal cells, macrophages, and fetal endothelial cells (FEC). Placental differentiation may be closely related to perinatal diseases, including fetal growth retardation (FGR) and hypertensive disorders of pregnancy (HDP), and miscarriage. There are limited findings regarding human chorionic villous differentiation and placental development because conducting in vivo studies is extremely difficult. Placental tissue varies widely among species. Thus, experimental animal findings are difficult to apply to humans. Early villous differentiation is difficult to study due to the small tissue size; however, a detailed analysis can potentially elucidate perinatal disease causes or help develop novel therapies. Artificial induction of early villous differentiation using human embryonic stem (ES) cells/induced pluripotent stem (iPS) cells was attempted, producing normally differentiated villi that can be used for interventional/invasive research. Here, we summarized and correlated early villous differentiation findings and discussed clinical diseases.
Topics: Animals; Chorionic Villi; Endothelial Cells; Female; Fetal Growth Retardation; Humans; Placenta; Placentation; Pregnancy; Trophoblasts
PubMed: 35887349
DOI: 10.3390/ijms23148003 -
Biology of Reproduction Jul 2021It is very difficult to gain a better understanding of the events in human pregnancy that occur during and just after implantation because such pregnancies are not yet... (Review)
Review
It is very difficult to gain a better understanding of the events in human pregnancy that occur during and just after implantation because such pregnancies are not yet clinically detectable. Animal models of human placentation are inadequate. In vitro models that utilize immortalized cell lines and cells derived from trophoblast cancers have multiple limitations. Primary cell and tissue cultures often have limited lifespans and cannot be obtained from the peri-implantation period. We present here two contemporary models of human peri-implantation placental development: extended blastocyst culture and stem-cell derived trophoblast culture. We discuss current research efforts that employ these models and how such models might be used in the future to study the "black box" stage of human pregnancy.
Topics: Blastocyst; Embryo Implantation; Female; Humans; Placentation; Pregnancy; Stem Cells; Trophoblasts
PubMed: 33899095
DOI: 10.1093/biolre/ioab080 -
Advances in Anatomy, Embryology, and... 2021In the domestic dog, placentation arises from central implantation, passing through a transitional, yet important stage of choriovitelline placenta (yolk sac placenta),...
In the domestic dog, placentation arises from central implantation, passing through a transitional, yet important stage of choriovitelline placenta (yolk sac placenta), on the way to the formation of the definite, deciduate, zonary (girdle) allantochorionic endotheliochorial placenta.Sharing some similarities with other invasive types of placentation, e.g., by revealing decidualization, it is characterized by restricted (shallow) invasion of trophoblast not affecting maternal capillaries and maternal decidual cells. Thus, being structurally and functionally placed between noninvasive epitheliochorial placentation and the more invasive hemochorial type, it presents an interesting and important model for understanding the evolutionarily determined aspects of mammalian placentation. More profound insights into the biological mechanisms underlying the restricted invasion of the fetal trophoblast into maternal uterine structures and the role of decidual cells in that process could provide better understanding of some adverse conditions occurring in humans, like preeclampsia or placenta accreta. As an important endocrine organ actively responding to ovarian steroids and producing its own hormones, e.g., serving as the source of gestational relaxin or prepartum prostaglandins, the canine placenta has become an attractive research target, both in basic and clinical research. In particular, the placental feto-maternal communication between maternal stroma-derived decidual cells and fetal trophoblast cells (i.e., an interplay between placenta materna and placenta fetalis) during the maintenance and termination of canine pregnancy serves as an interesting model for induction of parturition in mammals and is an attractive subject for translational and comparative research. Here, an updated view on morpho-functional aspects associated with canine placentation is presented.
Topics: Animals; Dogs; Embryo Implantation; Female; Placenta; Placentation; Pregnancy; Trophoblasts; Uterus
PubMed: 34694481
DOI: 10.1007/978-3-030-77360-1_8 -
Physiological Reviews Oct 2016Epidemiological evidence links an individual's susceptibility to chronic disease in adult life to events during their intrauterine phase of development. Biologically... (Review)
Review
Epidemiological evidence links an individual's susceptibility to chronic disease in adult life to events during their intrauterine phase of development. Biologically this should not be unexpected, for organ systems are at their most plastic when progenitor cells are proliferating and differentiating. Influences operating at this time can permanently affect their structure and functional capacity, and the activity of enzyme systems and endocrine axes. It is now appreciated that such effects lay the foundations for a diverse array of diseases that become manifest many years later, often in response to secondary environmental stressors. Fetal development is underpinned by the placenta, the organ that forms the interface between the fetus and its mother. All nutrients and oxygen reaching the fetus must pass through this organ. The placenta also has major endocrine functions, orchestrating maternal adaptations to pregnancy and mobilizing resources for fetal use. In addition, it acts as a selective barrier, creating a protective milieu by minimizing exposure of the fetus to maternal hormones, such as glucocorticoids, xenobiotics, pathogens, and parasites. The placenta shows a remarkable capacity to adapt to adverse environmental cues and lessen their impact on the fetus. However, if placental function is impaired, or its capacity to adapt is exceeded, then fetal development may be compromised. Here, we explore the complex relationships between the placental phenotype and developmental programming of chronic disease in the offspring. Ensuring optimal placentation offers a new approach to the prevention of disorders such as cardiovascular disease, diabetes, and obesity, which are reaching epidemic proportions.
Topics: Animals; Chronic Disease; Female; Fetal Development; Humans; Maternal-Fetal Exchange; Placenta; Placentation; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 27604528
DOI: 10.1152/physrev.00029.2015