Many toxicants are released into our ecosystems and environment every day, causing harmful effects on wildlife and the human population. Vinclozolin is an agricultural fungicide used in vegetable and fruit production and has been shown to cause irreversible effects in infertility cases. Although this fungicide helps prevent molds, blights, and rots, the compound has an anti-androgenic effect, blocking the androgen receptors of the male. Vinclozolin was stopped in the European Union in 2006, but it is still being used and distributed in the United States. Recent work has shown that this fungicide affects the transgenerational (F3) generations more than the directly exposed generations (F0, F1, F2). While the directly exposed F0 generations do not have any onset effects, the later generations that are transgenerational suffer as they have no say in whether they want to be ancestrally exposed to such harmful toxicants. The stability of the epigenetic transgenerational inheritance from ancestral exposures will be investigated. In the proposed research, since transgenerational generations are given no choice and are thus left to deal with the effects passed onto them, the ethics of such effects is also considered. This thesis tests the hypothesis that “environmental toxicants released into the environment can ancestrally affect the organism's germline cells to cause the epigenetic transgenerational inheritance of germline epimutations which allows the stable generational transmission of transgenerational epimutations in all subsequent generations.” A gestating female (F0 generation) was exposed to the toxicant vinclozolin. This toxicant exposure promotes transgenerational epigenetic traits and phenotypes of infertility, obesity, and other organ pathologies and diseases. The germline cells develop these epimutations in the epigenome, to promote the increase in infertility, obesity, and other organ disease phenotypes. We will use a transgenerational inheritance model of ancestral exposure to investigate the transgenerational stability of epigenetic inheritance. This will be investigated through ancestral exposure of the F0 generation to the toxicant vinclozolin and analysis in transgenerational models of 10 and 20 generations in mammals for generational stability.
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Title
GENERATIONAL STABILITY OF ENVIRONMENTALLY INDUCED EPIGENETIC TRANSGENERATIONAL INHERITANCE OF ADULT-ONSET DISEASE OVER TEN AND TWENTY GENERATIONS
Creators
Alexandra A. Korolenko
Contributors
Michael K. Skinner (Chair)
Patrick A. Carter (Committee Member)
Liam E. Broughton-Neiswanger (Committee Member)
Awarding Institution
Washington State University
Academic Unit
School of Biological Sciences
Theses and Dissertations
Doctor of Philosophy (PhD), Washington State University