The mechanism of action of 4-vinylcyclohexene diepoxide in the induction of ovarian toxicity.

Persistent Link:
http://hdl.handle.net/10150/186822
Title:
The mechanism of action of 4-vinylcyclohexene diepoxide in the induction of ovarian toxicity.
Author:
Flaws, Jodi Anne.
Issue Date:
1994
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:
Exposure of females to environmental chemicals can disrupt reproductive function by altering the normal functions of the oviducts, uterus, cervix, hypothalamus, anterior pituitary, or ovary. Compounds that directly affect the ovary can have a profound impact on fertility. Chemicals which destroy oocytes contained in primordial follicles cause early menopause and permanent infertility because only a finite number of these oocytes is contained within the ovary at birth and cannot be replaced. 4-vinylcyclohexene diepoxide (VCD) is one compound that has been shown to destroy oocytes contained in primordial follicles in rats and mice. The purpose of this dissertation was to determine: (1) the contribution of ovarian metabolism to VCD-induced oocyte depletion, (2) whether age is an important factor in the ability of VCD to disrupt reproduction, (3) the initial follicular and cellular target for destruction of oocytes by VCD, and (4) a possible mechanism by which VCD induces ovotoxicity. Data from this dissertation have shown that ovarian metabolism contributes to VCD-induced ovotoxicity because small pre-antral follicles (those follicles which are susceptible to VCD) were shown to have a reduced capacity to detoxify VCD compared to nontarget tissues such as large pre-antral follicles and hepatocytes. It has also been shown that age may not be an important factor in the ability of VCD to destroy oocytes because VCD destroyed oocytes to an equal extent in adult and immature rats. Age, however, was a factor in the ability of VCD to disrupt cyclicity and uterine function since reduced cyclicity and uterine weights were observed in adult, but not immature rats. Additionally, these studies have shown that the initial follicular target for VCD is the primordial follicle, 7-15 days of daily dosing are required to observe oocyte destruction, and VCD modulates secretion of a factor by granulosa cells that may lead to destruction of oocytes via inhibition of protein synthesis. Collectively, these studies have enhanced our understanding of factors which contribute to destruction of oocytes in small pre-antral follicles. Additionally, these studies have provided information regarding interactions of granulosa cells and oocytes contained in those follicles.
Type:
text; Dissertation-Reproduction (electronic)
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Physiological Sciences; Graduate College
Degree Grantor:
University of Arizona
Committee Chair:
Hoyer, Patricia B.

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleThe mechanism of action of 4-vinylcyclohexene diepoxide in the induction of ovarian toxicity.en_US
dc.creatorFlaws, Jodi Anne.en_US
dc.contributor.authorFlaws, Jodi Anne.en_US
dc.date.issued1994en_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.abstractExposure of females to environmental chemicals can disrupt reproductive function by altering the normal functions of the oviducts, uterus, cervix, hypothalamus, anterior pituitary, or ovary. Compounds that directly affect the ovary can have a profound impact on fertility. Chemicals which destroy oocytes contained in primordial follicles cause early menopause and permanent infertility because only a finite number of these oocytes is contained within the ovary at birth and cannot be replaced. 4-vinylcyclohexene diepoxide (VCD) is one compound that has been shown to destroy oocytes contained in primordial follicles in rats and mice. The purpose of this dissertation was to determine: (1) the contribution of ovarian metabolism to VCD-induced oocyte depletion, (2) whether age is an important factor in the ability of VCD to disrupt reproduction, (3) the initial follicular and cellular target for destruction of oocytes by VCD, and (4) a possible mechanism by which VCD induces ovotoxicity. Data from this dissertation have shown that ovarian metabolism contributes to VCD-induced ovotoxicity because small pre-antral follicles (those follicles which are susceptible to VCD) were shown to have a reduced capacity to detoxify VCD compared to nontarget tissues such as large pre-antral follicles and hepatocytes. It has also been shown that age may not be an important factor in the ability of VCD to destroy oocytes because VCD destroyed oocytes to an equal extent in adult and immature rats. Age, however, was a factor in the ability of VCD to disrupt cyclicity and uterine function since reduced cyclicity and uterine weights were observed in adult, but not immature rats. Additionally, these studies have shown that the initial follicular target for VCD is the primordial follicle, 7-15 days of daily dosing are required to observe oocyte destruction, and VCD modulates secretion of a factor by granulosa cells that may lead to destruction of oocytes via inhibition of protein synthesis. Collectively, these studies have enhanced our understanding of factors which contribute to destruction of oocytes in small pre-antral follicles. Additionally, these studies have provided information regarding interactions of granulosa cells and oocytes contained in those follicles.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplinePhysiological Sciencesen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.chairHoyer, Patricia B.en_US
dc.contributor.committeememberCarter, Dean E.en_US
dc.contributor.committeememberWise, Marken_US
dc.contributor.committeememberRacowsky, Catherineen_US
dc.identifier.proquest9502622en_US
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