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You searched for +publisher:"Wayne State University" +contributor:("D. Randall Armant"). Showing records 1 – 2 of 2 total matches.

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Wayne State University

1. Fritz, Rani. Trophoblast Retrieval And Isolation From The Cervix (tric) For Non-Invasive Prenatal Genetic Diagnosis And Prediction Of Abnormal Pregnancy Outcome.

Degree: PhD, Physiology, 2015, Wayne State University

The placenta is vital for the short- and long-term health of the fetus, and significantly impacts the health of the mother. During the first and second trimesters of pregnancy, extravillous trophoblast (EVT) cells invade the uterus and remodel the maternal spiral arteries, which, if inadequate, leads to pregnancy complications, including early pregnancy loss (EPL), preeclampsia (PE), and intra-uterine growth restriction (IUGR). EVT migration into the uterine wall is dependent on growth factors and cytokines that signal between maternal and fetal tissues. The epidermal growth factor (EGF) signaling system plays a significant role in trophoblast function. Using immunocytochemistry (ICC), we evaluated EGF family growth factors in post-partum PE placentas (villi and basal plate), and maternal serum, comparing gestational age (GA)-matched adverse preterm pregnancies and uncomplicated term pregnancies. EGF, heparin-binding EGF-like growth factor (HBEGF), and transforming growth factor alpha (TGFA) were significantly decreased in placentas from PE compared to IUGR, preterm labor, and uncomplicated term placentas. It was uncertain whether reduced growth factor signaling contributed to disease, or was the result of late-stage pathology. However, EGF was significantly reduced in prenatal serum of pregnant patients with PE compared to GA-matched patients without PE, demonstrating that the EGF signaling system is disrupted before PE symptoms dictate delivery. Currently, chorionic villous sampling is the only means by which intact placental cells can be obtained from an ongoing pregnancy. However, the earliest this invasive procedure can be preformed is 10 weeks GA, and it carries a risk of fetal loss. Trophoblast retrieval and isolation from the cervix (TRIC) can isolate intact trophoblast cells in a minimally invasive procedure from ongoing pregnancies as early as 5 weeks GA, using immunomagnetic isolation to target human leukocyte antigen-G, a protein present on trophoblast cells, but not on maternal cervical cells. ICC shows that the isolated cells are of the extravillous phenotype. The ability to isolate EVT cells from ongoing pregnancies not only provides clinicians with a tool to study the placenta in real time, but is also of benefit for prenatal genetic diagnosis (PGD). EVT protein expression was investigated, using TRIC with patient specimens obtained between 5-20 weeks GA. Using ICC, galectin 13 (LGALS13), galectin 14 (LGALS14), pregnancy-associated plasma protein-A (PAPPA), placental growth factor (PGF), endoglin (ENG), fms-like tyrosine kinase-1 (FLT1), and alpha-fetoprotein (AFP), proteins known to play a role in EVT function, were evaluated in EVT cells from patients that developed PE, IUGR, or EPL, and compared to pregnancies with uncomplicated term deliveries. Expression of LGALS14, PAPPA, and PGF significantly decreased in EVT cells from patients that developed IUGR, PE, or EPL, whereas expression of ENG, FLT1, and AFP were all significantly increased. To evaluate the… Advisors/Committee Members: D. Randall Armant.

Subjects/Keywords: Early Pregnancy Loss; Extravillous trophoblast cells; Placenta; Preeclampsia; Prenatal Diagnosis; Physiology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Fritz, R. (2015). Trophoblast Retrieval And Isolation From The Cervix (tric) For Non-Invasive Prenatal Genetic Diagnosis And Prediction Of Abnormal Pregnancy Outcome. (Doctoral Dissertation). Wayne State University. Retrieved from https://digitalcommons.wayne.edu/oa_dissertations/1310

Chicago Manual of Style (16th Edition):

Fritz, Rani. “Trophoblast Retrieval And Isolation From The Cervix (tric) For Non-Invasive Prenatal Genetic Diagnosis And Prediction Of Abnormal Pregnancy Outcome.” 2015. Doctoral Dissertation, Wayne State University. Accessed November 19, 2019. https://digitalcommons.wayne.edu/oa_dissertations/1310.

MLA Handbook (7th Edition):

Fritz, Rani. “Trophoblast Retrieval And Isolation From The Cervix (tric) For Non-Invasive Prenatal Genetic Diagnosis And Prediction Of Abnormal Pregnancy Outcome.” 2015. Web. 19 Nov 2019.

Vancouver:

Fritz R. Trophoblast Retrieval And Isolation From The Cervix (tric) For Non-Invasive Prenatal Genetic Diagnosis And Prediction Of Abnormal Pregnancy Outcome. [Internet] [Doctoral dissertation]. Wayne State University; 2015. [cited 2019 Nov 19]. Available from: https://digitalcommons.wayne.edu/oa_dissertations/1310.

Council of Science Editors:

Fritz R. Trophoblast Retrieval And Isolation From The Cervix (tric) For Non-Invasive Prenatal Genetic Diagnosis And Prediction Of Abnormal Pregnancy Outcome. [Doctoral Dissertation]. Wayne State University; 2015. Available from: https://digitalcommons.wayne.edu/oa_dissertations/1310


Wayne State University

2. Jain, Chandni V. Molecular Regulation Of Trophoblast Survival During Placentation And Pathologies Of Placental Insufficiency.

Degree: PhD, Physiology, 2016, Wayne State University

HBEGF, is present in the uterus at the time of embryo implantation and protects first trimester TB cells from apoptosis and promotes their invasion. The hypertensive disease, PE, in which TB invasion of the uterine arteries is reduced and TB apoptosis is elevated, is characterized by a reduction in HBEGF expression. In this study using a first trimester cell line and villous explant culture key components involved in HBEGF survival signaling pathway were identified. Specific MMP inhibitors established the requirement for MMP2 in HBEGF shedding and upregulation. NGS identified a HIF regulated gene, HSPA6 (HSP70B’) and using specific inhibitors it was established that HSP70 regulates MMP2 mediated shedding of HBEGF at low O2 and is functional upstream of MAPKs signaling cascade. To further investigate HBEGF upregulation at low O2 using NGS and siRNA knockdown of DGCR8 it was demonstrated that other components of RISC may be involved in regulation of HBEGF mRNA translation. These findings suggest that trophoblast survival during early pregnancy requires this signaling pathway and disruption of any component could lead to placental insufficiency. However, a global platform is needed to study the pathophysiology of trophoblast cells and their role in placental insufficiency. TRIC is an innovative platform to noninvasively acquire fetal cells. DNA was extracted from fetal cells isolated from 20 specimens with gestational age as early at 5 weeks to 19 weeks. This was followed by targeted sequencing using the Forenseq (Illumina) platform to identify informative SNPs. Using the Forenseq software 89% ± 12% of the 94 SNPs were called correctly in the fetal samples. Using the STR analysis out of the 20 fetal samples, 9 males were confirmed. Therefore, TRIC not only provides fetal cells but also opens new venues of perinatal testing. TRIC provides ample RNA from isolated fetal cells for extensive transcriptomic analysis. Using qPCR it was demonstrated that the fetal cells have higher expression for EVT specific markers such as HLA-G and KRT7 and markers for invasion/migration such as CDH5 and MMP9, whereas the maternal cells have a higher expression for epithelial markers such as CDH1 and ITGA6. This suggests that not only are the fetal cells EVT like but may also undergo an epithelial mesenchymal transition. Comparison of fetal and maternal cells from normal group using NGS identified 409 genes, of which top 5 upregulated and downregulated genes were validated by qPCR. Pathway analysis of the differentially regulated identified pathways related to… Advisors/Committee Members: D. Randall Armant.

Subjects/Keywords: HBEGF; oxygen; placenta; survival; TRIC; trophoblast; Other Astrophysics and Astronomy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Jain, C. V. (2016). Molecular Regulation Of Trophoblast Survival During Placentation And Pathologies Of Placental Insufficiency. (Doctoral Dissertation). Wayne State University. Retrieved from https://digitalcommons.wayne.edu/oa_dissertations/1642

Chicago Manual of Style (16th Edition):

Jain, Chandni V. “Molecular Regulation Of Trophoblast Survival During Placentation And Pathologies Of Placental Insufficiency.” 2016. Doctoral Dissertation, Wayne State University. Accessed November 19, 2019. https://digitalcommons.wayne.edu/oa_dissertations/1642.

MLA Handbook (7th Edition):

Jain, Chandni V. “Molecular Regulation Of Trophoblast Survival During Placentation And Pathologies Of Placental Insufficiency.” 2016. Web. 19 Nov 2019.

Vancouver:

Jain CV. Molecular Regulation Of Trophoblast Survival During Placentation And Pathologies Of Placental Insufficiency. [Internet] [Doctoral dissertation]. Wayne State University; 2016. [cited 2019 Nov 19]. Available from: https://digitalcommons.wayne.edu/oa_dissertations/1642.

Council of Science Editors:

Jain CV. Molecular Regulation Of Trophoblast Survival During Placentation And Pathologies Of Placental Insufficiency. [Doctoral Dissertation]. Wayne State University; 2016. Available from: https://digitalcommons.wayne.edu/oa_dissertations/1642

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