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2 edition of Human trophoblast cell death in pathological and physiological models of hypoxia found in the catalog.

Human trophoblast cell death in pathological and physiological models of hypoxia

Nima Soleymanlou

Human trophoblast cell death in pathological and physiological models of hypoxia

by Nima Soleymanlou

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Published .
Written in English


About the Edition

The second chapter shows that increased trophoblast cell death in preeclampsia is due to expression of Mtd-P, a novel pro-apoptotic splice variant of Matador (Mtd), a cell death inducing Bcl-2 family member. Mtd-P expression, resulting from exon II-skipping, increases under conditions of placental hypoxia/oxidative stress and is responsible for inducing apoptotic-mediated trophoblast cell death.Preeclampsia is a leading cause of maternal and fetal morbidity and death. This placental disease is characterized by reduced uteroplacental oxygenation; an event potentially responsible for increased trophoblast cell death. This pathologic insult is believed to contribute to the molecular events leading to the clinical manifestations of this disease. Hence, it is of paramount importance to study the impact of oxygenation on placental gene expression and to understand the regulation of molecules governing cell death pathways in placental pathology.Using high-throughput functional genomics, the first chapter of this dissertation demonstrates that global gene expression profiles obtained from in vitro and in vivo models of human placental hypoxia have a striking similarity to the profile of placental tissues obtained from preeclamptic pregnancies. These results represent the first molecular proof that global gene expression changes in preeclamptic pregnancies are due to placental hypoxia and that these events can successfully be mimicked in vitro and in vivo.The third chapter reports that aberrant placental oxygenation compromises the anti-apoptotic function of Mcl-1, the only interacting partner of Mtd. Notably, hypoxia-reoxygenation in vitro results in caspase-3-mediated Mcl-1 cleavage and induction of pro apoptotic Mcl-1 isoform expression, events that are only observed in severe early-onset preeclamptic placentae.Finally, studies in chapter four reveal that the pro-apoptotic function of Mtd-P cannot be antagonized by the anti-apoptotic Mcl-1L molecule. This lack of inhibition allows Mtd-P to cause trophoblast cell death and impair trophoblast cell fusion.The present body of work demonstrates that reduced oxygenation impacts global placental gene expression in preeclampsia and likely results in an imbalance in the Mtd-Mcl1 apoptotic rheostat, hence causing increased trophoblast cell death and impaired differentiation. As such, these molecular events may be important contributors leading to the pathogenesis of preeclampsia.

Edition Notes

Statementby Nima Soleymanlou.
The Physical Object
Paginationxvii, 272 leaves.
Number of Pages272
ID Numbers
Open LibraryOL19758398M
ISBN 109780494159323

Wingless ligands, a family of secreted proteins, are critically involved in organ development and tissue homeostasis by ensuring balanced rates of stem cell proliferation, cell death and differentiation. Wnt signaling components also play crucial roles in murine placental development controlling trophoblast lineage determination, chorioallantoic fusion and placental branching morphogenesis. Human embryonic stem (ES) cells have the potential to form any cell type, but ironically, the first cell lineage to form during development still represents a surprising challenge. The first cell type to become specialized is an epithelial cell that later defines the boundary between the embryo and mother for the formation of the placenta.

Mechanisms of initial cell fate decisions differ among species. To gain insights into lineage allocation in humans, we derived ten human embryonic stem cell lines (designated UCSFB) from single blastomeres of four 8-cell embryos and one cell embryo from a single couple. Compared with numerous conventional lines from blastocysts, they had unique gene expression and DNA methylation. Control of human trophoblast function. Reproductive Biology and Endocrinology. ;5(1) generation of distinct trophoblast cell types begins, namely the villous and the extravillous trophoblast, the former of which is devoted to fetal-maternal exchanges and the latter binds the placental body to the uterine wall. Physiological.

Culturing Trophoblast Stem (TS) Cell Lines Janet Rossant This protocol was adapted from "Isolation and Culture of Blastocyst-Derived Stem Cell Lines," Chapter 8 (Protocol 8, provided by the laboratory of Janet Rossant), in Manipulating the Mouse Embryo, 3rd edition, by Andras Nagy, Marina Gertsenstein, Kristina Vintersten, and Richard Behringer. Trophoblast: Definition, Importance, Cell Lines, Lesions and Gestational Trophoblastic Diseases by Dr. Cameron Troup MD in Cells They are the specialized cells of the placenta, they play a major role in the implantation and formation of the maternal-fetal interface.


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Human trophoblast cell death in pathological and physiological models of hypoxia by Nima Soleymanlou Download PDF EPUB FB2

The trophoblast cell lines have been removed from their in vivo environment for many passages and some of their properties may be distorted.

Regardless, they are commonly used as a convenient and valuable resource to provide insight into trophoblast function. A list of commonly used human trophoblast cell lines is provided in Table   Many of the studies providing evidence for hypoxia promoting an invasive trophoblast phenotype use the extravillous trophoblast hybrid cell line HTR-8/SVneo, as a substitute for extravillous trophoblasts which are difficult to propagate in culture, and whether this cell line truly reflects the behaviour of normal trophoblasts is open to by:   Live-cell imaging is a powerful tool that is widely used to investigate many physiological or pathological processes in various animal models or humans; however, to our knowledge, the mechanism of trophoblast cell fusion has not been reported using a live- cell imaging by: An invasive trophoblast cell lineage remodels uterine spiral arteries, facilitating nutrient flow, failure of which is associated with pathological conditions such as preeclampsia, intrauterine.

Intrauterine growth restriction, human placental development and trophoblast cell death Article Literature Review in The Journal of Physiology (Pt 14) June with 41 Reads. These alterations generate situations of hypoxia and hypoxia/reoxygenation (H/R) and consequent oxidative stress, increased cell death, and inflammation in trophoblasts.

The models used to understand the effects of hypoxia and H/R on trophoblasts require a rather big structure. Trophoblast development is a complex process involving dynamic changes in the expression and activity of transcription factors.

It is clear that transcription factors have critical roles in regulating all stages of trophoblast development (Table 1).However, transcription factors rarely work alone; rather, they operate in concert with chromatin remodeling factors, histone-modifying enzymes, and.

During early human pregnancy, extravillous cytotrophoblasts (CTBs) from anchoring villi invade the decidualized endometrium and myometrium (interstitial trophoblasts) and also migrate in a retrograde direction along the spiral arteries (endovascular trophoblasts) transforming them into large diameter conduit vessels of low resistance.

1 Endovascular trophoblast invasion has been reported to. Lack of Consensus over Definition of Trophoblast. We previously studied some “trophoblast” cell lines but were unable to confidently identify any of them as trophoblast (King et al., ).We have now updated these findings and collated published criteria used to characterize “trophoblast” cells derived from placentas or other cell types (hESC and fibroblasts) (Tables 1 and.

Clinical significance. The invasion of a specific type of trophoblast (extravillous trophoblast) into the maternal uterus is a vital stage in the establishment of e of the trophoblast to invade sufficiently is important in the development of some cases of firm of an attachment may lead to placenta accreta.

Gestational trophoblastic disease is a pregnancy. Studies using villous trophoblast cell in primary culture and villous explants show that hypoxia and hypoxia/reoxygenation systematically decrease trophoblast cell viability, concomitant with increased levels of oxidative stress, inflammation, autophagy and apopto This hypoxia/reoxygenation cell culture model, specifically, has.

The trophoblast, i.e. the peripheral part of the human conceptus, exerts a crucial role in implantation and placentation. Both processes properly occur as a consequence of an intimate dialogue between fetal and maternal tissues, fulfilled by membrane ligands and receptors, as well as by hormone and local factor release.

During blastocyst implantation, generation of distinct trophoblast cell. trophoblast [trof´o-blast] the peripheral cells of the blastocyst, which attach the zygote (fertilized ovum) to the uterine wall and become the placenta and the membranes that nourish and protect the developing organism.

The inner cellular layer is the cytotrophoblast and the outer layer is the syntrophoblast. trophoblast (trof'ō-blast, trō'fō. () This treatment regimen is based on the Trophoblastic Theory of cancer. This theory was originally proposed by a Scottish embryologist named John Beard (), and was resurrected by William Donald Kelley, DDS ().() Above Left Image: Placenta anatomic diagram from Gray’s Anatomy published in Trophoblasts as a specific cell lineage are crucial for the correct function of the placenta.

Human trophoblast stem cells (hTSCs) are a proliferative population that can differentiate into syncytiotrophoblasts and extravillous cytotrophoblasts. Many studies have reported that chemical supplements induce the differentiation of trophoblasts from human induced pluripotent stem cells.

From Trophoblasts to Human Placenta Harvey Kliman Sunday, Octo Page 4 of 19 Figure 2. Blastocyst. By days after fertilization the embryo has differentiated into two distinct cell types: inner cell mass (lighter cells)—which will develop into the fetus and eventually become the newborn and trophoblasts (darker cells)—which.

This page relates to proteins expressed by trophoblast cells during syncitial development and implantation. This page is more detailed than a general description of trophoblast cells, see Trophoblast for a general introduction to this cell type.

Many studies use animal models, term placenta or some new in vitro cell models. Developmental cell biology of human villous trophoblast: current research problems JOHN D.

APLIN* Maternal and Fetal Health Research Group, University of Manchester, UK ABSTRACT The common gestational pathologies are placental and developmental in origin. However, much remains to be learned about the key events of morphogenesis and growth in the.

The implantation process involves complex and synchronized molecular and cellular events between the uterus and the implanting embryo. These events are regulated by paracrine and autocrine factors.

Trophoblast invasion and migration through the uterine wall is mediated by molecular and cellular interactions, controlled by the trophoblast and the maternal microenvironment.

Chapter 53 ~ The Trophoblastic Theory of Cancer. The trophoblast cell is a cell derived from the Placenta, a structure inside the uterus of a pregnant mother which serves as blood supply for the developing embryo.

These trophoblast cells are known to produce human chorionic gonadotropin (HCG). In fact, production of HCG is the basis for. Mouse trophoblast stem cells (mTSCs), which were first derived over a decade ago, are a powerful cell culture model for studying their self-renewal or differentiation.

Our attempts to isolate an equivalent population from the trophectoderm of human blastocysts generated colonies that quickly differentiated in .Pluripotent human embryonic stem (hES) cells can differentiate into various cell types derived from the three embryonic germ layers and extraembryonic tissues such as trophoblasts.

The mechanisms governing lineage choices of hES cells are largely unknown. Here, we report that we established two independent hES cell clones lacking a group of cell surface molecules, glycosyl-phosphatidyl.T1 - Isolation of functional human trophoblast cells and their partial characterization in primary cell culture.

AU - Stromberg, Kurt. AU - Azizkhan, J. C. AU - Speeg, K. V. PY - /7/1. Y1 - /7/1.