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Seminars in Cell & Developmental Biology Nov 2022The placenta is a transient fetal organ that plays a critical role in the health and wellbeing of both the fetus and its mother. Functionally, the placenta sustains the... (Review)
Review
The placenta is a transient fetal organ that plays a critical role in the health and wellbeing of both the fetus and its mother. Functionally, the placenta sustains the growth of the fetus as it facilitates delivery of oxygen and nutrients and removal of waste products. Not surprisingly, defective early placental development is the primary cause of common disorders of pregnancy, including recurrent miscarriage, fetal growth restriction, pre-eclampsia and stillbirth. Adverse pregnancy conditions will also affect the life-long health of the fetus via developmental programming[1]. Despite its critical importance in reproductive success and life-long health, our understanding of placental development is not extensive, largely due to ethical limitations to studying early or chronological placental development, lack of long-term in vitro models, or comparative animal models. In this review, we examine current knowledge of early human placental development, discuss the critical role of the maternal endometrium and of the fetal-maternal dialogue in pregnancy success, and we explore the latest models of trophoblast and endometrial stem cells. In addition, we discuss the role of oxygen in placental formation and function, how nutrient delivery is mediated during the periods of histotrophic nutrition (uptake of uterine secretions) and haemotrophic nutrition (exchange between the maternal and fetal circulations), and how placental endocrine function facilitates fetal growth and development.
Topics: Animals; Female; Fetal Development; Humans; Maternal-Fetal Exchange; Oxygen; Placenta; Placentation; Pregnancy
PubMed: 35393235
DOI: 10.1016/j.semcdb.2022.03.039 -
Cellular and Molecular Life Sciences :... Sep 2019Abnormal placentation is considered as an underlying cause of various pregnancy complications such as miscarriage, preeclampsia and intrauterine growth restriction, the... (Review)
Review
Abnormal placentation is considered as an underlying cause of various pregnancy complications such as miscarriage, preeclampsia and intrauterine growth restriction, the latter increasing the risk for the development of severe disorders in later life such as cardiovascular disease and type 2 diabetes. Despite their importance, the molecular mechanisms governing human placental formation and trophoblast cell lineage specification and differentiation have been poorly unravelled, mostly due to the lack of appropriate cellular model systems. However, over the past few years major progress has been made by establishing self-renewing human trophoblast stem cells and 3-dimensional organoids from human blastocysts and early placental tissues opening the path for detailed molecular investigations. Herein, we summarize the present knowledge about human placental development, its stem cells, progenitors and differentiated cell types in the trophoblast epithelium and the villous core. Anatomy of the early placenta, current model systems, and critical key regulatory factors and signalling cascades governing placentation will be elucidated. In this context, we will discuss the role of the developmental pathways Wingless and Notch, controlling trophoblast stemness/differentiation and formation of invasive trophoblast progenitors, respectively.
Topics: Cardiovascular Diseases; Cell Differentiation; Diabetes Mellitus, Type 2; Female; Humans; Models, Biological; Placenta; Placentation; Pregnancy; Signal Transduction; Trophoblasts
PubMed: 31049600
DOI: 10.1007/s00018-019-03104-6 -
Fertility and Sterility Mar 2021Certain miscarriages result from immunologic factors, but there is no clear identification of the precise causes of recurrent pregnancy loss (RPL). Miscarriages and RPL... (Review)
Review
Certain miscarriages result from immunologic factors, but there is no clear identification of the precise causes of recurrent pregnancy loss (RPL). Miscarriages and RPL can arise from a disruption of maternal-fetal immune homeostasis. Remodeling of the maternal uterine spiral arteries is one of the key steps for normal growth and development of the fetus. An adequate oxygen supply is necessary for correct placentation, and it is accomplished by proper vascular changes. The development of fetal tissues creates a potential immunologic problem since the fetus can express paternal antigens and, in some cases, antigens of a gamete donor. The maternal immune system actively responds to fetal antigens, and dysregulation of this crosstalk could partly explain pregnancy complications such as miscarriages and RPL. RPL resulting from thrombophilia is primarily due to acquired thrombophilia, and therefore screening and treatment should be focused on antiphospholipid antibody syndrome.
Topics: Abortion, Habitual; Female; Humans; Immune Tolerance; Immunologic Factors; Placentation; Pregnancy; Thrombophilia
PubMed: 33610320
DOI: 10.1016/j.fertnstert.2021.01.017 -
International Journal of Molecular... Jan 2023Placentation is an immunological compromise where maternal immune system cells and trophoblastic cells interact to reach an equilibrium condition. Although the cross... (Review)
Review
Placentation is an immunological compromise where maternal immune system cells and trophoblastic cells interact to reach an equilibrium condition. Although the cross talk between the two systems is complex and not completely understood, Human Leukocyte Antigen G (HLA-G), expressed on trophoblastic cell surfaces, seems to be one of the main molecules involved in the modulation of both local and systemic maternal immune response. The prevalence of recurrent pregnancy loss (RPL), probably underestimated, is 5% of all women who achieve pregnancy, and about 40-60% percent of RPL cases are unexplained. There is an immunological analogy between allograft rejection and miscarriage, and the purpose of this review is to describe how the HLA-G pathway alterations are involved in disrupting the immunologic balance and in increasing the risk of recurrent pregnancy loss.
Topics: Pregnancy; Female; Humans; HLA-G Antigens; Abortion, Habitual; Placentation; Trophoblasts
PubMed: 36768880
DOI: 10.3390/ijms24032557 -
Modern Pathology : An Official Journal... Dec 2020The terminology and diagnostic criteria presently used by pathologists to report invasive placentation is inconsistent and does not reflect current knowledge of the... (Review)
Review
The terminology and diagnostic criteria presently used by pathologists to report invasive placentation is inconsistent and does not reflect current knowledge of the pathogenesis of the disease or the needs of the clinical care team. A consensus panel was convened to recommend terminology and reporting elements unified across the spectrum of PAS specimens (i.e., delivered placenta, total or partial hysterectomy with or without extrauterine tissues, curetting for retained products of conception). The proposed nomenclature under the umbrella diagnosis of placenta accreta spectrum (PAS) replaces the traditional categorical terminology (placenta accreta, increta, percreta) with a descriptive grading system that parallels the guidelines endorsed by the International Federation of Gynaecology and Obstetrics (FIGO). In addition, the nomenclature for hysterectomy specimens is separated from that for delivered placentas. The goal for each element in the system of nomenclature was to provide diagnostic criteria and guidelines for expected use in clinical practice.
Topics: Biopsy; Consensus; Documentation; Female; Forms and Records Control; Humans; Hysterectomy; Medical Records; Pathology, Clinical; Placenta; Placenta Accreta; Placentation; Predictive Value of Tests; Pregnancy; Severity of Illness Index; Terminology as Topic
PubMed: 32415266
DOI: 10.1038/s41379-020-0569-1 -
Cellular and Molecular Life Sciences :... May 2022Correct development of the human placenta and its differentiated epithelial cells, syncytial trophoblasts (STBs) and extravillous trophoblasts (EVTs), is crucial for a... (Review)
Review
Correct development of the human placenta and its differentiated epithelial cells, syncytial trophoblasts (STBs) and extravillous trophoblasts (EVTs), is crucial for a successful pregnancy outcome. STBs develop by cell fusion of mononuclear cytotrophoblasts (CTBs) in placental floating villi, whereas migratory EVTs originate from specialized villi anchoring to the maternal decidua. Defects in trophoblast differentiation have been associated with severe pregnancy disorders such as early-onset preeclampsia and fetal growth restriction. However, the evolutionary pathways underlying normal and adverse placentation are poorly understood. Herein, we discuss Wingless (WNT) and NOTCH signaling, two pathways that play pivotal roles in human placenta and trophoblast development. Whereas WNT is necessary for expansion of trophoblast progenitors and stem cells, NOTCH1 is required for proliferation and survival of EVT precursors. Differentiation of the latter is orchestrated by a switch in NOTCH receptor expression as well as by changes in WNT ligands and their downstream effectors.
Topics: Cell Differentiation; Female; Humans; Placenta; Placentation; Pregnancy; Receptors, Notch; Trophoblasts
PubMed: 35562545
DOI: 10.1007/s00018-022-04285-3 -
Cell Reports May 2023Here, we report that a chemical cocktail (LCDM: leukemia inhibitory factor [LIF], CHIR99021, dimethinedene maleate [DiM], minocycline hydrochloride), previously...
Here, we report that a chemical cocktail (LCDM: leukemia inhibitory factor [LIF], CHIR99021, dimethinedene maleate [DiM], minocycline hydrochloride), previously developed for extended pluripotent stem cells (EPSCs) in mice and humans, enables de novo derivation and long-term culture of bovine trophoblast stem cells (TSCs). Bovine TSCs retain developmental potency to differentiate into mature trophoblast cells and exhibit transcriptomic and epigenetic (chromatin accessibility and DNA methylome) features characteristic of trophectoderm cells from early bovine embryos. The bovine TSCs established in this study will provide a model to study bovine placentation and early pregnancy failure.
Topics: Pregnancy; Humans; Female; Animals; Cattle; Mice; Trophoblasts; Cell Differentiation; Pluripotent Stem Cells; Placentation
PubMed: 37146606
DOI: 10.1016/j.celrep.2023.112439 -
International Journal of Molecular... Jun 2020Interventions to prevent pregnancy complications have been largely unsuccessful. We suggest this is because the foundation for a healthy pregnancy is laid prior to the... (Review)
Review
Interventions to prevent pregnancy complications have been largely unsuccessful. We suggest this is because the foundation for a healthy pregnancy is laid prior to the establishment of the pregnancy at the time of endometrial decidualization. Humans are one of only a few mammalian viviparous species in which decidualization begins during the latter half of each menstrual cycle and is therefore independent of the conceptus. Failure to adequately prepare (decidualize) the endometrium hormonally, biochemically, and immunologically in anticipation of the approaching blastocyst-including the downregulation of genes involved in the pro- inflammatory response and resisting tissue invasion along with the increased expression of genes that promote angiogenesis, foster immune tolerance, and facilitate tissue invasion-leads to abnormal implantation/placentation and ultimately to adverse pregnancy outcome. We hypothesize, therefore, that the primary driver of pregnancy health is the quality of the soil, not the seed.
Topics: Animals; Autocrine Communication; Biomarkers; Decidua; Embryo Implantation; Endometrium; Female; Gene Expression Regulation; Humans; Paracrine Communication; Placentation; Pregnancy; Pregnancy Complications; Pregnancy Outcome
PubMed: 32521725
DOI: 10.3390/ijms21114092 -
American Journal of Obstetrics and... Feb 2022Physiological transformation with remodeling of the uteroplacental spiral arteries is key to a successful placentation and normal placental function. It is an intricate... (Review)
Review
Physiological transformation with remodeling of the uteroplacental spiral arteries is key to a successful placentation and normal placental function. It is an intricate process that involves, but is not restricted to, complex interactions between maternal decidual immune cells and invasive trophoblasts in the uterine wall. In normal pregnancy, the smooth muscle cells of the arterial tunica media of uteroplacental spiral arteries are replaced by invading trophoblasts and fibrinoid, and the arterial diameter increases 5- to 10-fold. Poor remodeling of the uteroplacental spiral arteries is linked to early-onset preeclampsia and several other major obstetrical syndromes, including fetal growth restriction, placental abruption, and spontaneous preterm premature rupture of membranes. Extravillous endoglandular and endovenous trophoblast invasions have recently been put forth as potential contributors to these syndromes as well. The well-acknowledged disturbed extravillous invasion of maternal spiral arteries in preeclampsia is summarized, as are briefly novel concepts of disturbed extravillous endoglandular and endovenous trophoblast invasions. Acute atherosis is a foam cell lesion of the uteroplacental spiral arteries associated with poor remodeling. It shares some morphologic features with early stages of atherosclerosis, but several molecular differences between these lesions have also recently been revealed. Acute atherosis is most prevalent at the maternal-fetal interface, at the tip of the spiral arteries. The localization of acute atherosis downstream of poorly remodeled arteries suggests that alterations in blood flow may trigger inflammation and foam cell development. Acute atherosis within the decidua basalis is not, however, confined to unremodeled areas of spiral arteries or to hypertensive disorders of pregnancy and may even be present in some clinically uneventful pregnancies. Given that foam cells of atherosclerotic lesions are known to arise from smooth muscle cells or macrophages activated by multiple types of inflammatory stimulation, we have proposed that multiple forms of decidual vascular inflammation may cause acute atherosis, with or without poor remodeling and/or preeclampsia. Furthermore, we propose that acute atherosis may develop at different gestational ages, depending on the type and degree of the inflammatory insult. This review summarizes the current knowledge of spiral artery remodeling defects and acute atherosis in preeclampsia. Some controversies will be presented, including endovascular and interstitial trophoblast invasion depths, the concept of 2-stage trophoblast invasion, and whether the replacement of maternal spiral artery endothelium by fetal endovascular trophoblasts is permanent. We will discuss the role of acute atherosis in the pathophysiology of preeclampsia and short- and long-term health correlates. Finally, we suggest future opportunities for research on this intriguing uteroplacental interface between the mother and fetus.
Topics: Atherosclerosis; Decidua; Female; Humans; Placenta; Placentation; Pre-Eclampsia; Pregnancy; Trophoblasts; Uterine Artery; Vascular Remodeling
PubMed: 32971013
DOI: 10.1016/j.ajog.2020.09.026 -
Cellular and Molecular Life Sciences :... Jun 2022Human pregnancy depends on the proper development of the embryo prior to implantation and the implantation of the embryo into the uterine wall. During the... (Review)
Review
Human pregnancy depends on the proper development of the embryo prior to implantation and the implantation of the embryo into the uterine wall. During the pre-implantation phase, formation of the morula is followed by internalization of blastomeres that differentiate into the pluripotent inner cell mass lineage, while the cells on the surface undergo polarization and differentiate into the trophectoderm of the blastocyst. The trophectoderm mediates apposition and adhesion of the blastocyst to the uterine epithelium. These processes lead to a stable contact between embryonic and maternal tissues, resulting in the formation of a new organ, the placenta. During implantation, the trophectoderm cells start to differentiate and form the basis for multiple specialized trophoblast subpopulations, all of which fulfilling specific key functions in placentation. They either differentiate into polar cells serving typical epithelial functions, or into apolar invasive cells that adapt the uterine wall to progressing pregnancy. The composition of these trophoblast subpopulations is crucial for human placenta development and alterations are suggested to result in placenta-associated pregnancy pathologies. This review article focuses on what is known about very early processes in human reproduction and emphasizes on morphological and functional aspects of early trophoblast differentiation and subpopulations.
Topics: Blastocyst; Cell Differentiation; Embryo Implantation; Female; Humans; Placenta; Placentation; Pregnancy; Trophoblasts
PubMed: 35661923
DOI: 10.1007/s00018-022-04377-0