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Studies on the regulation of normal ...

Chavez, Shawn L.

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Studies on the regulation of normal trophoblast apoptosis and survival during pregnancy.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Studies on the regulation of normal trophoblast apoptosis and survival during pregnancy./
Author:	Chavez, Shawn L.
Description:	189 p.
Notes:	Source: Dissertation Abstracts International, Volume: 67-04, Section: B, page: 1900.
Contained By:	Dissertation Abstracts International67-04B.
Subject:	Biology, Molecular. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3214191
ISBN:	9780542651397

Studies on the regulation of normal trophoblast apoptosis and survival during pregnancy.
Chavez, Shawn L.

Studies on the regulation of normal trophoblast apoptosis and survival during pregnancy. - 189 p.

Source: Dissertation Abstracts International, Volume: 67-04, Section: B, page: 1900.

Thesis (Ph.D.)--Yale University, 2006.

Apoptosis is important for normal placental development, but it may also be involved in the pathophysiology of pregnancy-related diseases. Normal placental development is dependent upon the differentiation and invasion of the trophoblast, the main cellular component of the placenta. Trophoblast apoptosis increases in normal placentas as gestations proceeds and a greater incidence of trophoblast apoptosis has been observed in pregnancies complicated by preeclampsia or intrauterine growth restriction (IUGR). This suggests that alterations in the regulation of trophoblast apoptosis may contribute to the pathological conditions associated with abnormal pregnancy.

ISBN: 9780542651397Subjects--Topical Terms:

1017719
Biology, Molecular.

Studies on the regulation of normal trophoblast apoptosis and survival during pregnancy.
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035 $a (UMI)AAI3214191
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100 1 $a Chavez, Shawn L. $3 1917885
245 1 0 $a Studies on the regulation of normal trophoblast apoptosis and survival during pregnancy.
300 $a 189 p.
500 $a Source: Dissertation Abstracts International, Volume: 67-04, Section: B, page: 1900.
500 $a Advisers: Gil Mor; Harold Behrman.
502 $a Thesis (Ph.D.)--Yale University, 2006.
520 $a Apoptosis is important for normal placental development, but it may also be involved in the pathophysiology of pregnancy-related diseases. Normal placental development is dependent upon the differentiation and invasion of the trophoblast, the main cellular component of the placenta. Trophoblast apoptosis increases in normal placentas as gestations proceeds and a greater incidence of trophoblast apoptosis has been observed in pregnancies complicated by preeclampsia or intrauterine growth restriction (IUGR). This suggests that alterations in the regulation of trophoblast apoptosis may contribute to the pathological conditions associated with abnormal pregnancy.
520 $a In order to understand the pathophysiology of pregnancy complications and develop new potential treatments for pregnancy-related diseases, it is necessary to know how normal trophoblast apoptosis and survival is regulated. Therefore, the focus of my research is to elucidate the intracellular apoptotic pathways mediating trophoblast cell apoptosis, identify and characterize novel regulators of apoptosis and determine differences in the regulation of trophoblast apoptosis between normal and abnormal pregnancies.
520 $a The Fas/Fast system represents one of the main apoptotic pathways controlling trophoblast apoptosis. First trimester trophoblast cells express both Fas and FasL, but do not undergo apoptosis upon Fas stimulation. Here, I present data demonstrating both in vivo and in vitro that trophoblast resistance to FasL-induced apoptosis is due to the expression of X-linked Inhibitor of Apoptosis (XIAP), an intracellular protein that prevents caspase activation downstream of Fas stimulation. Additionally, I also provide evidence that the PI3K/Akt (protein kinase B) survival pathway protects trophoblast cells from Fas-mediated apoptosis by regulating the expression and function of XIAP.
520 $a In contrast to FasL, first trimester trophoblast cells are sensitive to TNF-alpha-induced apoptosis, suggesting that TNF-alpha may activate an alternative pathway. My work reveals that the pro-apoptotic nuclear protein, XIAP-Associated Factor 1 (XAF1), promotes TNF-alpha-mediated trophoblast apoptosis by acting through the mitochondrial pathway, thereby inhibiting the anti-caspase activity of XIAP. I also present data showing that XAF1 is regulated at the mRNA level by TNF-alpha. These findings suggest a novel mechanism by which first trimester trophoblast cells are sensitive to TNF-alpha, but resistant to FasL-induced apoptosis.
590 $a School code: 0265.
650 4 $a Biology, Molecular. $3 1017719
650 4 $a Health Sciences, Obstetrics and Gynecology. $3 1020690
650 4 $a Health Sciences, Human Development. $3 1019218
690 $a 0307
690 $a 0380
690 $a 0758
710 2 0 $a Yale University. $3 515640
773 0 $t Dissertation Abstracts International $g 67-04B.
790 1 0 $a Mor, Gil, $e advisor
790 1 0 $a Behrman, Harold, $e advisor
790 $a 0265
791 $a Ph.D.
792 $a 2006
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3214191