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Cell Adhesion & Migration Mar 2016Trophoblast migration and invasion through the decidua and maternal uterine spiral arteries are crucial events in placentation. During this process, invasive trophoblast... (Comparative Study)
Comparative Study Review
Trophoblast migration and invasion through the decidua and maternal uterine spiral arteries are crucial events in placentation. During this process, invasive trophoblast replace vascular endothelial cells as the uterine arteries are remodeled to form more permissive vessels that facilitate adequate blood flow to the growing fetus. Placentation failures resulting from either extensive or shallow trophoblastic invasion can cause pregnancy complications such as preeclampsia, intrauterine growth restriction, placenta creta, gestational trophoblastic disease and even maternal or fetal death. Consequently, the use of experimental animal models such as rats and mice has led to great progress in recent years with regards to the identification of mechanisms and factors that control trophoblast migration kinetics. This review aims to perform a comparative analysis of placentation and the mechanisms and factors that coordinate intrauterine trophoblast migration in humans, rats and mice under physiological and pathological conditions.
Topics: Animals; Cell Differentiation; Cell Movement; Female; Humans; Models, Biological; Pregnancy; Rodentia; Stress, Physiological; Trophoblasts; Uterus
PubMed: 26743330
DOI: 10.1080/19336918.2015.1120397 -
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 -
International Journal of Molecular... Dec 2019Historically, invasion of placental trophoblasts was thought to be extremely specific, only invading into the connective tissues of the maternal uterus and finally... (Review)
Review
Historically, invasion of placental trophoblasts was thought to be extremely specific, only invading into the connective tissues of the maternal uterus and finally reaching and transforming the uterine spiral arteries. Only recently, identification of new routes of trophoblast invasion into different structures of the maternal uterus has been achieved. Thorough morphological analysis has resulted in the identification of trophoblasts invading into glands, veins, and lymph vessels of the uterine wall. These new routes pave the way for a re-evaluation of trophoblast invasion during normal placental development. Of course, such new routes of trophoblast invasion may well be altered, especially in pregnancy pathologies such as intra-uterine growth restriction, preeclampsia, early and recurrent pregnancy loss, stillbirth, and spontaneous abortion. Maybe one or more of these pregnancy pathologies show alterations in different pathways of trophoblast invasion, and, thus, etiologies may need to be redefined, and new therapies may be developed.
Topics: Abortion, Habitual; Female; Fetal Growth Retardation; Humans; Placentation; Pre-Eclampsia; Pregnancy; Trophoblasts
PubMed: 31906245
DOI: 10.3390/ijms21010289 -
Frontiers in Immunology 2021The immune tolerance microenvironment is crucial for the establishment and maintenance of pregnancy at the maternal-fetal interface. The maternal-fetal interface is a... (Review)
Review
The immune tolerance microenvironment is crucial for the establishment and maintenance of pregnancy at the maternal-fetal interface. The maternal-fetal interface is a complex system containing various cells, including lymphocytes, decidual stromal cells, and trophoblasts. Macrophages are the second-largest leukocytes at the maternal-fetal interface, which has been demonstrated to play essential roles in remodeling spiral arteries, maintaining maternal-fetal immune tolerance, and regulating trophoblast's biological behaviors. Many researchers, including us, have conducted a series of studies on the crosstalk between macrophages and trophoblasts at the maternal-fetal interface: on the one hand, macrophages can affect the invasion and migration of trophoblasts; on the other hand, trophoblasts can regulate macrophage polarization and influence the state of the maternal-fetal immune microenvironment. In this review, we systemically introduce the functions of macrophages and trophoblasts and the cell-cell interaction between them for the establishment and maintenance of pregnancy. Advances in this area will further accelerate the basic research and clinical translation of reproductive medicine.
Topics: Animals; Cell Communication; Cell Movement; Cellular Microenvironment; Cytokines; Extracellular Vesicles; Female; Fetus; Humans; Immune Tolerance; Macrophage Activation; Macrophages; Mice; Pregnancy; Trophoblasts
PubMed: 34745133
DOI: 10.3389/fimmu.2021.758281 -
Nature Reviews. Immunology Apr 2023The role of the maternal immune system in reproductive success in humans remains controversial. Here we focus on the events that occur in the maternal decidua during the... (Review)
Review
The role of the maternal immune system in reproductive success in humans remains controversial. Here we focus on the events that occur in the maternal decidua during the first few weeks of human pregnancy, because this is the site at which maternal leukocytes initially interact with and can recognize fetal trophoblast cells, potentially involving allorecognition by both T cells and natural killer (NK) cells. NK cells are the dominant leukocyte population in first-trimester decidua, and genetic studies point to a role of allorecognition by uterine NK cells in establishing a boundary between the mother and the fetus. By contrast, definitive evidence that allorecognition by decidual T cells occurs during the first trimester is lacking. Thus, our view is that during the crucial period when the placenta is established, damaging T cell-mediated adaptive immune responses towards placental trophoblast are minimized, whereas NK cell allorecognition contributes to successful implantation and healthy pregnancy.
Topics: Pregnancy; Humans; Female; Trophoblasts; Placenta; Decidua; Pregnancy Trimester, First; Killer Cells, Natural
PubMed: 36192648
DOI: 10.1038/s41577-022-00777-2 -
Cell Cycle (Georgetown, Tex.) Jul 2012Hemochorial placentation is characterized by extensive remodeling of the maternal vasculature, converting them to flaccid low resistance vessels. This process greatly... (Review)
Review
Hemochorial placentation is characterized by extensive remodeling of the maternal vasculature, converting them to flaccid low resistance vessels. This process greatly facilitates exchange of nutrients and gases between the mother and the fetus. Two key modulators that orchestrate these vascular changes have been identified at the maternal fetal interface, natural killer (NK) cells and invasive trophoblast cells. Hypoxia-inducible factor (HIF) transcription factors direct cellular responses to low oxygen, influencing trophoblast lineage commitment and promoting development of the invasive trophoblast lineage. This short review focuses on role of NK cells on uterine spiral artery development and subsequent modulation of oxygen tensions at the maternal fetal interface.
Topics: Basic Helix-Loop-Helix Transcription Factors; Cell Differentiation; Female; Humans; Hypoxia; Killer Cells, Natural; Maternal-Fetal Exchange; Placenta; Pregnancy; Trophoblasts
PubMed: 22659845
DOI: 10.4161/cc.20542 -
Reproduction (Cambridge, England) Jul 2020Appropriate human trophoblast lineage specification and differentiation is crucial for the establishment of normal placentation and maintenance of pregnancy. However,... (Review)
Review
Appropriate human trophoblast lineage specification and differentiation is crucial for the establishment of normal placentation and maintenance of pregnancy. However, due to the lack of proper modeling systems, the molecular mechanisms of these processes are still largely unknown. Much of the early studies in this area have been based on animal models and tumor-derived trophoblast cell lines, both of which are suboptimal for modeling this unique human organ. Recent advances in regenerative and stem cell biology methods have led to development of novel in vitro model systems for studying human trophoblast. These include derivation of human embryonic and induced pluripotent stem cells and establishment of methods for the differentiation of these cells into trophoblast, as well as the more recent derivation of human trophoblast stem cells. In addition, advances in culture conditions, from traditional two-dimensional monolayer culture to 3D culturing systems, have led to development of trophoblast organoid and placenta-on-a-chip model, enabling us to study human trophoblast function in context of more physiologically accurate environment. In this review, we will discuss these various model systems, with a focus on human trophoblast, and their ability to help elucidate the key mechanisms underlying placental development and function. This review focuses on model systems of human trophoblast differentiation, including advantages and limitations of stem cell-based culture, trophoblast organoid, and organ-on-a-chip methods and their applications in understanding placental development and disease.
Topics: Cell Differentiation; Epithelium; Female; Humans; Maternal-Fetal Exchange; Models, Biological; Placenta; Placentation; Pregnancy; Trophoblasts
PubMed: 32485667
DOI: 10.1530/REP-19-0428 -
Placenta Dec 2017Mammalian reproduction is critically dependent on trophoblast cells, which ensure embryo implantation and placentation. Development of trophoblast cell lineages is a... (Review)
Review
Mammalian reproduction is critically dependent on trophoblast cells, which ensure embryo implantation and placentation. Development of trophoblast cell lineages is a multi-step process and relies upon proper spatial and temporal gene expression, which is regulated by multiple transcription factors. However, most of the transcription factors that are implicated in trophoblast development regulate gene expression at a specific developmental stage or in a specific trophoblast subtype. In contrast, recent studies from our group and other laboratories indicate that conserved GATA family of transcription factors, GATA2 and GATA3, are important to regulate gene expression at multiple stages of trophoblast development. Furthermore, our conditional gene deletion studies revealed that functional redundancy of GATA2 and GATA3 ensures both self-renewal of trophoblast stem and progenitor cells and their differentiation to trophoblast cells of a matured placenta. Together these findings indicate that GATA2/GATA3 are the master orchestrators of gene expression in trophoblast cells and they fine tune gene regulatory network to establish distinct trophoblast cell types during placentation.
Topics: Animals; Blastocyst; Embryonic Development; Embryonic Stem Cells; Female; GATA Transcription Factors; Gene Expression Regulation, Developmental; Humans; Placenta; Placentation; Pregnancy; Pregnancy Complications; Trophoblasts
PubMed: 28526138
DOI: 10.1016/j.placenta.2017.05.005 -
Cell Adhesion & Migration Mar 2016The establishment of a functional placenta is pivotal for normal fetal development and the maintenance of pregnancy. In the course of early placentation, trophoblast... (Review)
Review
The establishment of a functional placenta is pivotal for normal fetal development and the maintenance of pregnancy. In the course of early placentation, trophoblast precursors differentiate into highly invasive trophoblast subtypes. These cells, referred to as extravillous trophoblasts (EVTs), penetrate the maternal uterus reaching as far as the inner third of the myometrium. One of the most fundamental functions of EVTs is the transformation of spiral arteries to establish the uteroplacental blood circulation assuring an adequate nutrient and gas supply to the developing fetus. To achieve this, specialized EVT subpopulations interact with maternal immune cells, provoke elastolysis in the arterial wall and replace the endothelial cells lining the spiral arteries to induce intraluminal vascular remodeling. These and other trophoblast-mediated processes are tightly controlled by paracrine signals from the maternal decidua and furthermore underlie an intrinsic cell-type specific program. Various severe pregnancy complications such as preeclampsia or intrauterine growth retardation are associated with abnormal EVT function, shallow invasion, and decreased blood flow to the placenta. Hence a better understanding of human trophoblast invasion seems mandatory to improve therapeutic intervention. This approach, however, requires a profound knowledge of the human placenta, its various trophoblast subtypes and in particular a better understanding of the regulatory network that controls the invasive phenotype of EVTs.
Topics: Cell Movement; Female; Humans; Models, Biological; Pregnancy; Trophoblasts
PubMed: 26418186
DOI: 10.1080/19336918.2015.1089376 -
Journal of Reproductive Immunology Dec 1997The human placenta serves as a barrier to the transmission of some viruses, but allows others to reach the fetal circulation. The resistance and permissiveness of the... (Review)
Review
The human placenta serves as a barrier to the transmission of some viruses, but allows others to reach the fetal circulation. The resistance and permissiveness of the placenta to viral transmission appears to be determined in large part by the placental trophoblast. In order to define the mechanisms by which human trophoblast cells influence vertical transmission of viruses, we have studied the interaction of replication-deficient recombinant viral vectors with transformed human choriocarcinoma (BeWo) cells and primary trophoblast cell cultures. Recombinant adenovirus vectors efficiently transduce BeWo cells and primary trophoblast cells. However, as BeWo cells differentiate after treatment with cAMP analogs, they become relatively resistant to adenovirus-mediated transduction due to diminished uptake of the virus particles. This differentiation-dependent loss of adenovirus transduction may be related to the down-regulation of the coxsackie adenovirus receptor, which we have detected in undifferentiated trophoblast cells. Recombinant herpes simplex virus vectors also transduce undifferentiated BeWo cells and isolated cytotrophoblast cells, but transduction by herpes simplex virus vectors declines with cAMP-induced trophoblast differentiation, apparently due to reduced viral uptake. In contrast, cAMP treatment augments trophoblast transduction by recombinant adeno-associated virus, a member of the parvovirus family. This augmentation appears to be due to increased virus uptake by a yet to be determined mechanism. The understanding of the molecular basis of these interactions between recombinant viral vectors and trophoblast cells may yield strategies to prevent vertical transmission of viruses as well as to create opportunities to modify trophoblast function through gene transfer using viral vectors.
Topics: Adenoviridae; Animals; Dependovirus; Female; Humans; Pregnancy; Simplexvirus; Trophoblasts; Virus Diseases; Virus Physiological Phenomena
PubMed: 9501288
DOI: 10.1016/s0165-0378(97)00071-5