Neonatal Exposure to the Phytoestrogen Genistein Alters Ovarian Differentiation and Development

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dc.contributor.advisor John Vandenbergh, Committee Member en_US
dc.contributor.advisor Johh Gadsby, Committee Member en_US
dc.contributor.advisor Gerald A. LeBlanc, Committee Chair en_US
dc.contributor.advisor Retha R. Newbold, Committee Member en_US
dc.contributor.advisor Ida Washington Smoak, Committee Member en_US Jefferson, Wendy Noble en_US 2010-04-02T18:49:05Z 2010-04-02T18:49:05Z 2006-01-17 en_US
dc.identifier.other etd-09262005-095720 en_US
dc.description.abstract Genistein, the primary phytoestrogen in soy, was investigated for potential adverse effects on the developing female reproductive system with particular focus on the ovary. Mice were treated with genistein at doses that span the range of human exposure including vegetarian mothers during pregnancy and lactation to infants on soy based infant formulas. Neonatal genistein exposure caused the formation of multi-oocyte follicles (MOFs) in the ovary. This effect is mediated by ERβ as mice lacking this receptor do not develop MOFs while mice lacking ERβ do. Further study of genistein's effects on the ovary revealed inhibition of neonatal oocyte nest breakdown; oocytes were still attached by intercellular bridges and the normal progression of apoptosis was attenuated. Mechanistic studies of MOF formation revealed alterations in cell adhesion molecules. In addition, genistein is not unique in its ability to cause ovarian disruption; other environmental estrogens caused MOFs as well as altered cell adhesion molecule expression. Further, these effects appear to be exacerbated by preferential binding to ERβ. Assessment of reproductive function showed that mice treated with genistein (0.5 and 5 mg/kg) showed signs of early reproductive senescence while mice treated with genistein (50 mg/kg) exhibited infertility characterized by fewer, smaller, implantation sites as well as reabsorptions; ovaries from these mice had no corpora lutea. Stimulation with exogenous gonadotropins restored ovulation, suggesting problems with the hypothalamic-gonadal axis. These data taken together demonstrate that neonatal exposure to genistein at environmentally relevant doses causes adverse effects on the developing reproductive system and in particular on the ovary. en_US
dc.rights I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to NC State University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. en_US
dc.subject estrogen en_US
dc.subject endocrine disruptor en_US
dc.subject reproduction en_US
dc.title Neonatal Exposure to the Phytoestrogen Genistein Alters Ovarian Differentiation and Development en_US PhD en_US dissertation en_US Toxicology en_US

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