The role of oxidative stress and nuclear factor-kappa B in the control of apoptosis and atresia in dominant bovine follicles

Persistent Link:
http://hdl.handle.net/10150/290132
Title:
The role of oxidative stress and nuclear factor-kappa B in the control of apoptosis and atresia in dominant bovine follicles
Author:
Valdez, Kelli E.
Issue Date:
2004
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Apoptosis of granulosa cells is an early feature of atresia in bovine follicles. However, the mechanisms initiating apoptosis of granulosa cells have not been well characterized. In many cell types, apoptosis can be induced by oxidative stress and prevented by increased expression of endogenous oxidative stress response proteins. The transcription factor nuclear factor-kappaB (NF-κB) regulates genes involved in preventing oxidative stress and has been characterized as a mediator of cell survival. Studies have suggested that NF-κB activity may be regulated by estradiol-17β, a major determinant of follicular health. Therefore, these studies tested the hypotheses that oxidative stress is involved in the atresia of non-ovulatory dominant bovine follicles and NF-κB suppresses apoptosis in the healthy dominant follicle. Because the onset of atresia during the first wave of follicular development following ovulation has previously been characterized in cattle, it provides an excellent model to study the relationship between apoptosis, oxidative stress response proteins, NF-kappaB, and estradiol production. Decreased production of estradiol was accompanied by increased numbers of non-viable granulosa cells in dominant follicles between Days 4 and 6 of the first follicular wave in cattle. Unexpectedly, expression of genes encoding oxidative stress response proteins in granulosa cells increased on Day 8 of the follicular wave, but did not translate into increased expression of the corresponding proteins or greater enzyme activity. The decline in estradiol production observed on Day 6 of the 1st follicular wave is not due to lack of androgen substrate or down-regulated expression of the aromatase gene, but instead appears to be the direct result of decreased activity of the aromatase enzyme within granulosa cells. Follicular NF-κB activation was associated with estradiol production. However, direct inhibition of NF-κB activity suppressed apoptosis of granulosa cells in vitro. Therefore, whether NF-κB is playing a pro- or anti-apoptotic role in granulosa cells of bovine follicles remains to be elucidated. These experiments begin to elucidate the signals that trigger the sequence of events leading to apoptosis and atresia of bovine follicles and provide the framework for future experiments designed to further clarify the complex interplay of signals that determine a follicle's fate.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Biology, Animal Physiology.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Physiological Sciences
Degree Grantor:
University of Arizona
Advisor:
Turzillo, Adele M.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleThe role of oxidative stress and nuclear factor-kappa B in the control of apoptosis and atresia in dominant bovine folliclesen_US
dc.creatorValdez, Kelli E.en_US
dc.contributor.authorValdez, Kelli E.en_US
dc.date.issued2004en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractApoptosis of granulosa cells is an early feature of atresia in bovine follicles. However, the mechanisms initiating apoptosis of granulosa cells have not been well characterized. In many cell types, apoptosis can be induced by oxidative stress and prevented by increased expression of endogenous oxidative stress response proteins. The transcription factor nuclear factor-kappaB (NF-κB) regulates genes involved in preventing oxidative stress and has been characterized as a mediator of cell survival. Studies have suggested that NF-κB activity may be regulated by estradiol-17β, a major determinant of follicular health. Therefore, these studies tested the hypotheses that oxidative stress is involved in the atresia of non-ovulatory dominant bovine follicles and NF-κB suppresses apoptosis in the healthy dominant follicle. Because the onset of atresia during the first wave of follicular development following ovulation has previously been characterized in cattle, it provides an excellent model to study the relationship between apoptosis, oxidative stress response proteins, NF-kappaB, and estradiol production. Decreased production of estradiol was accompanied by increased numbers of non-viable granulosa cells in dominant follicles between Days 4 and 6 of the first follicular wave in cattle. Unexpectedly, expression of genes encoding oxidative stress response proteins in granulosa cells increased on Day 8 of the follicular wave, but did not translate into increased expression of the corresponding proteins or greater enzyme activity. The decline in estradiol production observed on Day 6 of the 1st follicular wave is not due to lack of androgen substrate or down-regulated expression of the aromatase gene, but instead appears to be the direct result of decreased activity of the aromatase enzyme within granulosa cells. Follicular NF-κB activation was associated with estradiol production. However, direct inhibition of NF-κB activity suppressed apoptosis of granulosa cells in vitro. Therefore, whether NF-κB is playing a pro- or anti-apoptotic role in granulosa cells of bovine follicles remains to be elucidated. These experiments begin to elucidate the signals that trigger the sequence of events leading to apoptosis and atresia of bovine follicles and provide the framework for future experiments designed to further clarify the complex interplay of signals that determine a follicle's fate.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectBiology, Animal Physiology.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplinePhysiological Sciencesen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorTurzillo, Adele M.en_US
dc.identifier.proquest3145142en_US
dc.identifier.bibrecord.b47213243en_US
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