Effects of Perfluorinated Compounds on GnRH Gene Expression in vitro Public Deposited

http://ir.library.oregonstate.edu/concern/undergraduate_thesis_or_projects/j098zc66s

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  • Perfluorinated chemicals have been widely used in industry for their superior surfactant qualities. Because of their widespread usage and resistance to photolytic and biodegradation mechanisms, as well as their ability to undergo long-range atmospheric transport, these compounds have become ubiquitous in the world-wide water supplies. Of particular interest are perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), which have been demonstrated to be biological endpoint products that are capable of acting as estrogen mimetics. As estrogen itself plays a pivotal role in reproductive function in mammals, this study aimed to determine if and to what extent perfluoro chemicals disrupt normal patterns of gene expression of the neurohormone gonadotropin-releasing hormone (GnRH). By use of stably transfected secreteable reporter systems in immortalized GT1-7 neurons, a widely accepted in vitro model of GnRH neurons, effects of perfluoro chemicals on GnRH transcriptional activity were determined at concentrations of 10 and 20 μM PFOS or PFOA, as well as dose-response curves following in vitro exposure to 50 μM, 500 nM, 5 nM, 500 pM and 5 pM concentrations of PFOS, and 100 mM, 1 mM, 100 μM, 1 μM and 100 nM concentrations of PFOA. Apparent up-regulation of GnRH gene expression was observed in 1mM, 10μM, and 1μM concentration treatments of PFOA, and 5nM, 500pM and 5pM concentration treatments of PFOS. Apparent down-regulation of GnRH gene expression was noted in 50μM and 10μM PFOS, as well as 100mM PFOA. TUNEL assays were also performed to determine whether changes observed in gene expression rates could be attributed to induction of apoptosis. Increased percentages of cells in the apoptotic phase were observed in 100mM, 1mM, 1μM and 100nM PFOA treatment groups, as well as 50μM PFOS, vs. DMSO control. Apparent reduction in percentage of apoptotic cells was noted in 100μM PFOA, and 500nM, 5nM, 500pM and 5pM PFOS treatments.
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  • description.provenance : Submitted by Wanda Crannell (crannelw@hort.oregonstate.edu) on 2009-12-10T22:32:13Z No. of bitstreams: 4 BathkeseminarPresentation.pptx: 3783121 bytes, checksum: c41ddea139a413eb1380917cbfcf2923 (MD5) BathkeSignaturePageThesis.docx: 11357 bytes, checksum: 194c9fb5f567a03f0ef291f7d71af4bf (MD5) BathkeTitlePageThesis.docx: 10470 bytes, checksum: 5294aec2240c935f6b50b73c28360499 (MD5) BathkeFinal Thesis Draft.docx: 270819 bytes, checksum: 502582c91fd919b92ee3c513930b8be8 (MD5)
  • description.provenance : Approved for entry into archive by Linda Kathman(linda.kathman@oregonstate.edu) on 2009-12-14T23:33:54Z (GMT) No. of bitstreams: 4 BathkeseminarPresentation.pptx: 3783121 bytes, checksum: c41ddea139a413eb1380917cbfcf2923 (MD5) BathkeSignaturePageThesis.docx: 11357 bytes, checksum: 194c9fb5f567a03f0ef291f7d71af4bf (MD5) BathkeTitlePageThesis.docx: 10470 bytes, checksum: 5294aec2240c935f6b50b73c28360499 (MD5) BathkeFinal Thesis Draft.docx: 270819 bytes, checksum: 502582c91fd919b92ee3c513930b8be8 (MD5)
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