Sex and life stage sensitivity of rainbow trout to xenoestrogens Public Deposited

http://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/q237hv71v

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  • Numerous natural and anthropogenic chemicals interact with endocrine systems of animals. The most widely studied of these endocrine active chemicals (EACs) are estrogen receptor agonists and antagonists. Because of the many important roles of estrogens in animals, xenoestrogens have the potential to impact environmental health. It has been proposed that xenoestrogen contaminants are responsible for recent increases in estrogen dependent human diseases and sexual and developmental abnormalities in wildlife. Aquatic species are particularly susceptible to persistent EACs that accumulate in sediments and biomagnify along trophic levels. Rainbow trout, Oncorhynchus mykiss, commonly used in biomedical research and as a sentinel species, was chosen as a model for studying mechanisms of xenoestrogen activity. The aims of this research were to assess the estrogenic activity of individual persistent, organic contaminants and simple mixtures in vivo. Emphasis was placed on determining the potential for xenoestrogens to alter sexual development or to induce sexually dimorphic biochemical responses. Gonadal abnormalities in trout exposed as embryos to the xenoestrogen o,p'-DDE showed that xenobiotics can affect trout sexual development. However, the absence of endocrine disruption by low doses of o,p'-DDE, by the xenoestrogens chlordecone and octylphenol, or by the anti-androgen p,p'-DDE, suggested that lethality is likely to precede endocrine disruption in highly exposed, feral salmonid populations. Sexually distinct responses in immature trout were documented with respect to vitellogenin induction (2 to 4 fold higher in females) and cytochrome P450 expression. Sex differences occurred only when doses of estrogens or xenoestrogens were below levels that cause maximal estrogenic responses. Evidence suggests that estrogen regulation may be fundamentally different in immature males and females, which may have implications for natural populations exposed to xenoestrogens. Vitellogenin induction and P450 modulation were responsive to mixtures of estrogens and xenoestrogens in a manner suggestive of additive activation of estrogen receptors. Cytochrome P450 dependent induction of lauric acid hydroxylation was observed for the first time in trout, in response to tamoxifen and mixtures of tamoxifen and 17β-estradiol. The estrogenic activity of tamoxifen and 4-hydroxy-2',4',6'-trichlorobiphenyl were greater in vivo than what was predicted by in vitro studies, which emphasized the need for mechanism based investigations of xenoestrogens in whole organisms.
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