Date of Award

1-1-1998

Embargo Period

4-18-2024

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Molecular and Cellular Biology and Pathobiology

College

College of Graduate Studies

First Advisor

John S. Ramsdell

Second Advisor

Rick Pollenz

Third Advisor

Jim Norris

Fourth Advisor

Craig Sullivan

Fifth Advisor

Geoffrey I. Scott

Abstract

Several classes of environmental contaminants have been demonstrated to disrupt reproductive function in wild populations and laboratory animals through interactions with endocrine pathways. Primary targets for these endocrine active contaminants are steroid hormone receptors and steroidogenic enzymes. The first study tests the hypothesis that aromatase represents a major target for environmental contaminants which disrupt reproductive function. The results indicate that the biosynthesis of estrogens can be inhibited by certain pesticides and that aromatase represents a target for contaminants disrupting reproductive function. The second study develops an estrogen sensitive and specific reporter gene assay responsive to steroid hormones and several estrogenic contaminants, including pesticides and polychlorinated biphenyls (PCBs). Next, we test the hypothesis that environmental contaminants which demonstrate in vitro endocrine activity will alter normal fish sexual differentiation in vivo. The critical period of larval fish sex differentiation was targeted by directly microinjecting lipophilic endocrine active chemicals into fertilized eggs of d-rR strain medaka (Oryzias latipes). The exposure route models maternal to embryo transfer of lipophilic contaminants. An exposure of o,p'-DDT results in sex reversal of genetic males to phenotypic females (XY-females). Male to female sex reversal, upon o,p'-DDT exposure during gonad development, provides clear evidence to support the hypothesis that environmental contaminants with in vitro endocrine activity can alter sexual differentiation in vivo.

Rights

Copyright is held by the author. All rights reserved.

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