Inhibition of PIK3 Signaling Pathway Members by the Ovotoxicant 4-Vinylcyclohexene Diepoxide in Rats

dc.contributor.author Keating, Aileen
dc.contributor.author Fernandez, Shannon
dc.contributor.author Keating, Aileen
dc.contributor.author Mark-Kappeler, Connie
dc.contributor.author Sen, Nivedita
dc.contributor.author Sipes, I. Glenn
dc.contributor.author Hoyer, Patricia
dc.contributor.department Animal Science
dc.date 2019-09-22T22:39:09.000
dc.date.accessioned 2020-06-29T23:41:14Z
dc.date.available 2020-06-29T23:41:14Z
dc.date.copyright Sat Jan 01 00:00:00 UTC 2011
dc.date.issued 2011-04-01
dc.description.abstract <p>4-Vinylcyclohexene diepoxide (VCD), an occupational chemical that specifically destroys primordial and small primary follicles in the ovaries of rats and mice, is thought to target an oocyte-expressed tyrosine kinase receptor, Kit. This study compared the temporal effect of VCD on protein distribution of KIT and its downstream PIK3-activated proteins, AKT and FOXO3. Postnatal Day 4 Fischer 344 rat ovaries were cultured in control media ± VCD (30 μM) for 2–8 days (d2–d8). KIT, AKT, phosphorylated AKT, FOXO3, and pFOXO3 protein levels were assessed by Western blotting and/or immunofluorescence staining with confocal microscopy. Phosphorylated AKT was decreased (<em>P</em> < 0.05) in oocyte nuclei in primordial (39% decrease) and small primary (37% decrease) follicles within 2 days of VCD exposure. After d4, VCD reduced (<em>P</em> < 0.05) oocyte staining for KIT (primordial, 44% decrease; small primary, 39% decrease) and FOXO3 (primordial, 40% decrease; small primary, 36% decrease) protein. Total AKT and pFOXO3 were not affected by VCD at any time. <em>Akt1</em> mRNA, as measured by quantitative RT-PCR, was reduced (<em>P</em> < 0.05) by 23% on d4 of VCD exposure, but returned to control levels on d6 and d8. VCD exposure reduced <em>Foxo3a</em>mRNA by 26% on d6 (<em>P</em> < 0.05) and by 23% on d8 (<em>P</em> < 0.1). These results demonstrate that the earliest observed effect of VCD is an inhibition of phosphorylation and nuclear localization of AKT in the oocyte of primordial and small primary follicles. This event is followed by reductions in KIT and FOXO3 protein subcellular distribution prior to changes in mRNA. Thus, these findings further support that VCD induces ovotoxicity by directly targeting the oocyte through posttranslational inhibition of KIT-mediated signaling components.</p>
dc.description.comments <p>This article is published as Keating, Aileen F., Shannon M. Fernandez, Connie J. Mark-Kappeler, Nivedita Sen, I. Glenn Sipes, and Patricia B. Hoyer. "Inhibition of PIK3 signaling pathway members by the ovotoxicant 4-vinylcyclohexene diepoxide in rats." <em>Biology of reproduction</em> 84, no. 4 (2011): 743-751. doi: <a href="https://doi.org/10.1095/biolreprod.110.087650">10.1095/biolreprod.110.087650</a>.</p>
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dc.identifier archive/lib.dr.iastate.edu/ans_pubs/490/
dc.identifier.articleid 1491
dc.identifier.contextkey 15020913
dc.identifier.s3bucket isulib-bepress-aws-west
dc.identifier.submissionpath ans_pubs/490
dc.identifier.uri https://dr.lib.iastate.edu/handle/20.500.12876/9924
dc.language.iso en
dc.source.bitstream archive/lib.dr.iastate.edu/ans_pubs/490/2011_Keating_InhibitionSignaling.pdf|||Sat Jan 15 00:29:55 UTC 2022
dc.source.uri 10.1095/biolreprod.110.087650
dc.subject.disciplines Animal Experimentation and Research
dc.subject.disciplines Animal Sciences
dc.subject.disciplines Cellular and Molecular Physiology
dc.subject.disciplines Genetics
dc.subject.keywords follicle
dc.subject.keywords ovary
dc.subject.keywords toxicology
dc.title Inhibition of PIK3 Signaling Pathway Members by the Ovotoxicant 4-Vinylcyclohexene Diepoxide in Rats
dc.type article
dc.type.genre article
dspace.entity.type Publication
relation.isAuthorOfPublication abe31007-187a-4174-864e-6871e3f9a0d7
relation.isOrgUnitOfPublication 85ecce08-311a-441b-9c4d-ee2a3569506f
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