Cellular and molecular mechanisms of 4-vinylcyclohexene-diepoxide induced ovotoxicity in rats

Persistent Link:
http://hdl.handle.net/10150/282161
Title:
Cellular and molecular mechanisms of 4-vinylcyclohexene-diepoxide induced ovotoxicity in rats
Author:
Springer, Lisa Nicole, 1966-
Issue Date:
1996
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:
4-vinylcyclohexene diepoxide (VCD) is an environmental xenobiotic formed as a by-product in the manufacture of rubber and therefore potential human exposure is likely. VCD destroys half of the small pre-antral (25-100 μm) follicles in ovaries of rats following 15 days of dosing. The overall goal of this research, was to determine the mode and earliest time for identification of follicular destruction and examine the specificity of the response for 25-100 μm follicles. The particular involvement of protein synthesis and gene expression in this ovotoxic response was also examined. After daily dosing with VCD (80 mg/kg), the rate of protein synthesis in 25-100 μm follicles was inhibited following 3, 6, and 10 hr of in vitro incubation with VCD; whereas, the inhibition in the rate of protein synthesis at 3 hr in 25-100 μm follicles from untreated animals was reversed at 6 and 10 hr. Furthermore, follicular viability was compromised to a greater extent in 25-100 μm follicles from dosed versus untreated animals. Following 10 days of daily dosing with VCD, there was an increase in random DNA fragmentation in 25-100 μm follicles; however, there was not a reduction in the numbers of primordial and primary (25-100 μm) follicles. Morphological analysis showed changes characteristic of an apoptotic-like form of cell death in oocytes and granulosa cells of primordial and primary follicles 4 hr following 10 days of daily dosing. There was an increase in levels of mRNA for bax, manganese superoxide dismutase (MnSOD) and microsomal epoxide hydrolase (mEH) in 25-100 μm follicles following 10 days dosing with VCD, but the increase was not observed in large pre-antral (100-250 μm) follicles or liver. However, decreases in levels of mRNA for bax in liver and mEH in 100-250 μm follicles were observed. These results suggest that repeated dosing makes 25-100 μm follicles more susceptible to VCD-induced cellular changes and that VCD-induces an apoptotic-like form of cell death which is mediated through changes in levels of expression of genes associated with death of the follicular cells.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Biology, Cell.; Health Sciences, Toxicology.; Biology, Animal Physiology.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Physiological Sciences
Degree Grantor:
University of Arizona
Advisor:
Hoyer, Patricia B.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleCellular and molecular mechanisms of 4-vinylcyclohexene-diepoxide induced ovotoxicity in ratsen_US
dc.creatorSpringer, Lisa Nicole, 1966-en_US
dc.contributor.authorSpringer, Lisa Nicole, 1966-en_US
dc.date.issued1996en_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.abstract4-vinylcyclohexene diepoxide (VCD) is an environmental xenobiotic formed as a by-product in the manufacture of rubber and therefore potential human exposure is likely. VCD destroys half of the small pre-antral (25-100 μm) follicles in ovaries of rats following 15 days of dosing. The overall goal of this research, was to determine the mode and earliest time for identification of follicular destruction and examine the specificity of the response for 25-100 μm follicles. The particular involvement of protein synthesis and gene expression in this ovotoxic response was also examined. After daily dosing with VCD (80 mg/kg), the rate of protein synthesis in 25-100 μm follicles was inhibited following 3, 6, and 10 hr of in vitro incubation with VCD; whereas, the inhibition in the rate of protein synthesis at 3 hr in 25-100 μm follicles from untreated animals was reversed at 6 and 10 hr. Furthermore, follicular viability was compromised to a greater extent in 25-100 μm follicles from dosed versus untreated animals. Following 10 days of daily dosing with VCD, there was an increase in random DNA fragmentation in 25-100 μm follicles; however, there was not a reduction in the numbers of primordial and primary (25-100 μm) follicles. Morphological analysis showed changes characteristic of an apoptotic-like form of cell death in oocytes and granulosa cells of primordial and primary follicles 4 hr following 10 days of daily dosing. There was an increase in levels of mRNA for bax, manganese superoxide dismutase (MnSOD) and microsomal epoxide hydrolase (mEH) in 25-100 μm follicles following 10 days dosing with VCD, but the increase was not observed in large pre-antral (100-250 μm) follicles or liver. However, decreases in levels of mRNA for bax in liver and mEH in 100-250 μm follicles were observed. These results suggest that repeated dosing makes 25-100 μm follicles more susceptible to VCD-induced cellular changes and that VCD-induces an apoptotic-like form of cell death which is mediated through changes in levels of expression of genes associated with death of the follicular cells.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectBiology, Cell.en_US
dc.subjectHealth Sciences, Toxicology.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.advisorHoyer, Patricia B.en_US
dc.identifier.proquest9713391en_US
dc.identifier.bibrecord.b34387729en_US
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