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Nature Communications Feb 2024Proper placental development in early pregnancy ensures a positive outcome later on. The developmental relationship between the placenta and embryonic organs, such as...
Proper placental development in early pregnancy ensures a positive outcome later on. The developmental relationship between the placenta and embryonic organs, such as the heart, is crucial for a normal pregnancy. However, the mechanism through which the placenta influences the development of embryonic organs remains unclear. Trophoblasts fuse to form multinucleated syncytiotrophoblasts (SynT), which primarily make up the placental materno-fetal interface. We discovered that endogenous progesterone immunomodulatory binding factor 1 (PIBF1) is vital for trophoblast differentiation and fusion into SynT in humans and mice. PIBF1 facilitates communication between SynT and adjacent vascular cells, promoting vascular network development in the primary placenta. This process affected the early development of the embryonic cardiovascular system in mice. Moreover, in vitro experiments showed that PIBF1 promotes the development of cardiovascular characteristics in heart organoids. Our findings show how SynTs organize the barrier and imply their possible roles in supporting embryogenesis, including cardiovascular development. SynT-derived factors and SynT within the placenta may play critical roles in ensuring proper organogenesis of other organs in the embryo.
Topics: Animals; Female; Humans; Mice; Pregnancy; Cell Differentiation; Embryonic Development; Placenta; Placentation; Pregnancy Proteins; Suppressor Factors, Immunologic; Trophoblasts; Cardiovascular System
PubMed: 38374152
DOI: 10.1038/s41467-024-45647-8 -
International Journal of Molecular... Feb 2015The thyroid hormone, 3,3,5-triiodo-L-thyronine (T3), modulates several physiological processes, including cellular growth, differentiation, metabolism, inflammation and... (Review)
Review
The thyroid hormone, 3,3,5-triiodo-L-thyronine (T3), modulates several physiological processes, including cellular growth, differentiation, metabolism, inflammation and proliferation, via interactions with thyroid hormone response elements (TREs) in the regulatory regions of target genes. Infection and inflammation are critical processes in placental development and pregnancy-related diseases. In particular, infection is the leading cause of neonatal mortality and morbidity worldwide. However, to date, no successful approach has been developed for the effective diagnosis of infection in preterm infants. Pre-eclampsia (PE) is a serious disorder that adversely affects ~5% of human pregnancies. Recent studies identified a multiprotein complex, the inflammasome, including the Nod-like receptor (NLR) family of cytosolic pattern recognition receptors, the adaptor protein apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1, which plays a vital role in the placenta. The thyroid hormone modulates inflammation processes and is additionally implicated in placental development and disease. Therefore, elucidation of thyroid hormone receptor-regulated inflammation-related molecules, and their underlying mechanisms in placenta, should facilitate the identification of novel predictive and therapeutic targets for placental disorders. This review provides a detailed summary of current knowledge with respect to identification of useful biomarkers and their physiological significance in placenta.
Topics: Chemokines; Cytokines; Female; Humans; Inflammation; Placenta; Placenta Diseases; Placentation; Pregnancy; Receptors, Thyroid Hormone; Thyroid Hormones
PubMed: 25690032
DOI: 10.3390/ijms16024161 -
Reproductive Biology and Endocrinology... Jul 2004Based on the number of tissues separating maternal from fetal blood, placentas are classified as epitheliochorial, endotheliochorial or hemochorial. We review the... (Comparative Study)
Comparative Study Review
Based on the number of tissues separating maternal from fetal blood, placentas are classified as epitheliochorial, endotheliochorial or hemochorial. We review the occurrence of these placental types in the various orders of eutherian mammals within the framework of the four superorders identified by the techniques of molecular phylogenetics. The superorder Afrotheria diversified in ancient Africa and its living representatives include elephants, sea cows, hyraxes, aardvark, elephant shrews and tenrecs. Xenarthra, comprising armadillos, anteaters and sloths, diversified in South America. All placentas examined from members of these two oldest superorders are either endotheliochorial or hemochorial. The superorder Euarchontoglires includes two sister groups, Glires and Euarchonta. The former comprises rodents and lagomorphs, which typically have hemochorial placentas. The most primitive members of Euarchonta, the tree shrews, have endotheliochorial placentation. Flying lemurs and all higher primates have hemochorial placentas. However, the lemurs and lorises are exceptional among primates in having epitheliochorial placentation. Laurasiatheria, the last superorder to arise, includes several orders with epitheliochorial placentation. These comprise whales, camels, pigs, ruminants, horses and pangolins. In contrast, nearly all carnivores have endotheliochorial placentation, whilst bats have endotheliochorial or hemochorial placentas. Also included in Laurasiatheria are a number of insectivores that have many conserved morphological characters; none of these has epitheliochorial placentation. Consideration of placental type in relation to the findings of molecular phylogenetics suggests that the likely path of evolution in Afrotheria was from endotheliochorial to hemochorial placentation. This is also a likely scenario for Xenarthra and the bats. We argue that a definitive epitheliochorial placenta is a secondary specialization and that it evolved twice, once in the Laurasiatheria and once in the lemurs and lorises.
Topics: Animals; Female; Humans; Placentation; Pregnancy; Trophoblasts
PubMed: 15236656
DOI: 10.1186/1477-7827-2-46 -
Cellular and Molecular Life Sciences :... Jun 2022The use of in vitro tools to study trophoblast differentiation and function is essential to improve understanding of normal and abnormal placental development. The... (Review)
Review
The use of in vitro tools to study trophoblast differentiation and function is essential to improve understanding of normal and abnormal placental development. The relative accessibility of human placentae enables the use of primary trophoblasts and placental explants in a range of in vitro systems. Recent advances in stem cell models, three-dimensional organoid cultures, and organ-on-a-chip systems have further shed light on the complex microenvironment and cell-cell crosstalk involved in placental development. However, understanding each model's strengths and limitations, and which in vivo aspects of human placentation in vitro data acquired does, or does not, accurately reflect, is key to interpret findings appropriately. To help researchers use and design anatomically accurate culture models, this review both outlines our current understanding of placental development, and critically considers the range of established and emerging culture models used to study this, with a focus on those derived from primary tissue.
Topics: Cell Differentiation; Female; Humans; Placenta; Placentation; Pregnancy; Stem Cells; Trophoblasts
PubMed: 35753002
DOI: 10.1007/s00018-022-04407-x -
Development (Cambridge, England) Jun 2023The placenta is essential for reproductive success. The murine placenta includes polyploid giant cells that are crucial for its function. Polyploidy occurs broadly in...
The placenta is essential for reproductive success. The murine placenta includes polyploid giant cells that are crucial for its function. Polyploidy occurs broadly in nature but its regulators and significance in the placenta are unknown. We have discovered that many murine placental cell types are polyploid and have identified factors that license polyploidy using single-cell RNA sequencing. Myc is a key regulator of polyploidy and placental development, and is required for multiple rounds of DNA replication, likely via endocycles, in trophoblast giant cells. Furthermore, MYC supports the expression of DNA replication and nucleotide biosynthesis genes along with ribosomal RNA. Increased DNA damage and senescence occur in trophoblast giant cells without Myc, accompanied by senescence in the neighboring maternal decidua. These data reveal Myc is essential for polyploidy to support normal placental development, thereby preventing premature senescence. Our study, combined with available literature, suggests that Myc is an evolutionarily conserved regulator of polyploidy.
Topics: Animals; Female; Mice; Pregnancy; Placenta; Placentation; Polyploidy; Trophoblasts
PubMed: 37278344
DOI: 10.1242/dev.201581 -
Reproductive Sciences (Thousand Oaks,... Sep 2021In recent years, a growing interest has arisen regarding the possible relationship between adverse pregnancy outcomes (APOs) and inadequate maternal hemodynamic... (Review)
Review
In recent years, a growing interest has arisen regarding the possible relationship between adverse pregnancy outcomes (APOs) and inadequate maternal hemodynamic adaptations to the pregnancy. A possible association between "placental syndromes," such as preeclampsia (PE) and fetal growth restriction (FGR), and subsequent maternal cardiovascular diseases (CVD) later in life has been reported. The two subtypes of FGR show different pathogenetic and clinical features. Defective placentation, due to a poor trophoblastic invasion of the maternal spiral arteries, is believed to play a central role in the pathogenesis of early-onset PE and FGR. Since placental functioning is dependent on the maternal cardiovascular system, a pre-existent or subsequent cardiovascular impairment may play a key role in the pathogenesis of early-onset FGR. Late FGR does not seem to be determined by a primary abnormal placentation in the first trimester. The pathological pathway of late-onset FGR may be due to a primary maternal cardiovascular maladaptation: CV system shows a flat profile and remains similar to those of non-pregnant women. Since the second trimester, when the placenta is already developed and increases its functional request, a hypovolemic state could lead to placental hypoperfusion and to an altered maturation of the placental villous tree and therefore to an altered fetal growth. Thus, this review focalizes on the possible relationship between maternal cardiac function and placentation in the development of both early and late-onset FGR. A better understanding of maternal hemodynamics in pregnancies complicated by FGR could bring various benefits in clinical practice, improving screening and therapeutic tools.
Topics: Adaptation, Physiological; Animals; Female; Fetal Growth Retardation; Hemodynamics; Humans; Maternal-Fetal Exchange; Models, Cardiovascular; Placenta; Placental Circulation; Placentation; Pregnancy; Risk Assessment; Risk Factors
PubMed: 33211274
DOI: 10.1007/s43032-020-00393-2 -
International Journal of Molecular... Sep 2022Galectins (Gal) are characterized by their affinity for galactoside structures on glycoconjugates. This relationship is mediated by carbohydrate recognition domains,... (Review)
Review
Galectins (Gal) are characterized by their affinity for galactoside structures on glycoconjugates. This relationship is mediated by carbohydrate recognition domains, which are multifunctional regulators of basic cellular biological processes with high structural similarity among family members. They participate in both innate and adaptive immune responses, as well as in reproductive immunology. Recently, the discovery that galectins are highly expressed at the maternal-fetal interface has garnerd the interest of experts in human reproduction. Galectins are involved in a variety of functions such as maternal-fetal immune tolerance, angiogenesis, trophoblast invasion and placental development and are considered to be important mediators of successful embryo implantation and during pregnancy. Dysregulation of these galectins is associated with abnormal and pathological pregnancies (e.g., preeclampsia, gestational diabetes mellitus, fetal growth restriction, preterm birth). Our work reviews the regulatory mechanisms of galectins in normal and pathological pregnancies and has implications for clinicians in the prevention, diagnosis and treatment of pregnancy-related diseases.
Topics: Female; Galectins; Humans; Infant, Newborn; Placenta; Placentation; Pregnancy; Premature Birth; Trophoblasts
PubMed: 36077508
DOI: 10.3390/ijms231710110 -
ELife Sep 2017Eutherians are often mistakenly termed 'placental mammals', but marsupials also have a placenta to mediate early embryonic development. Lactation is necessary for both...
Eutherians are often mistakenly termed 'placental mammals', but marsupials also have a placenta to mediate early embryonic development. Lactation is necessary for both infant and fetal development in eutherians and marsupials, although marsupials have a far more complex milk repertoire that facilitates morphogenesis of developmentally immature young. In this study, we demonstrate that the anatomically simple tammar placenta expresses a dynamic molecular program that is reminiscent of eutherian placentation, including both fetal and maternal signals. Further, we provide evidence that genes facilitating fetal development and nutrient transport display convergent co-option by placental and mammary gland cell types to optimize offspring success.
Topics: Animals; Biological Evolution; Eutheria; Female; Gene Expression Regulation, Developmental; Lactation; Mammary Glands, Animal; Mice; Milk; Placenta; Placentation; Pregnancy
PubMed: 28895534
DOI: 10.7554/eLife.27450 -
Journal of Human Hypertension Aug 2022Recent advances have been made in understanding the nature of placental dysfunction causing preeclampsia, and other hypertensive disorders of pregnancy. The contribution... (Review)
Review
Recent advances have been made in understanding the nature of placental dysfunction causing preeclampsia, and other hypertensive disorders of pregnancy. The contribution of animal studies in the understanding of the effects of inadequate placentation on blood pressure and other target organs will be explored in this review. This will include technical aspects of animal studies in pregnancy, as well as the translation of data regarding newly discovered pathological pathways, in particular the angiogenic pathway, into targets in clinical practice.
Topics: Animals; Blood Pressure; Female; Humans; Models, Animal; Placenta; Placentation; Pre-Eclampsia; Pregnancy
PubMed: 34837033
DOI: 10.1038/s41371-021-00637-x -
Physiological Genomics Aug 2022Preeclampsia (PE), a pregnancy-specific disorder, is characterized by maternal hypertension and proteinuria or another accompanying sign/symptom of multiorgan... (Review)
Review
Preeclampsia (PE), a pregnancy-specific disorder, is characterized by maternal hypertension and proteinuria or another accompanying sign/symptom of multiorgan dysfunction. Maternal symptoms resolve with delivery of the baby and, importantly, the placenta. Therefore, the placenta plays a causal role in PE. However, the precise cause of abnormal placental development and/or function is unknown. Women with obesity have an increased risk of developing PE that is potentially related to the increased inflammation that accompanies increased maternal adiposity. Furthermore, inflammatory adipokines, i.e., leptin, have been linked to the development of systemic inflammation, hypertension, and other adverse outcomes associated with PE. Rodent models that recapitulate key pathophysiological features of the maternal and fetal syndrome have been used translationally to study PE. This review covers inflammatory adipokines, immune cells, and impaired placental development associated with PE in women and in rodent models of PE that use functional genomics to test causation.
Topics: Adipokines; Adipose Tissue; Female; Humans; Hypertension; Inflammation; Obesity; Placenta; Placentation; Pre-Eclampsia; Pregnancy
PubMed: 35816649
DOI: 10.1152/physiolgenomics.00041.2022