Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/80331
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dc.contributor.authorFullston, T.en
dc.contributor.authorOhlsson Teague, E.en
dc.contributor.authorMc Pherson, N.en
dc.contributor.authorDe Blasio, M.en
dc.contributor.authorMitchell, M.en
dc.contributor.authorCorbett, M.en
dc.contributor.authorPrint, C.en
dc.contributor.authorOwens, J.en
dc.contributor.authorLane, M.en
dc.date.issued2013en
dc.identifier.citationFASEB Journal, 2013; 27(10):4226-4243en
dc.identifier.issn0892-6638en
dc.identifier.issn1530-6860en
dc.identifier.urihttp://hdl.handle.net/2440/80331-
dc.descriptionPublished online before print July 11, 2013en
dc.description.abstractObesity is highly prevalent, and its incidence is increasing. The previous study showing a major effect of paternal obesity on metabolic health of offspring is confounded by comorbidity with diabetes. Therefore, we investigated the effect of diet-induced paternal obesity, in the absence of diabetes, on the metabolic health of two resultant generations and the molecular profiles of the testes and sperm. Founder (F0) male C57BL6 mice were fed either a high-fat diet (HFD) or a control diet (CD); n = 10/diet for a period of 10 wk. Testis expression of mRNA/microRNAs was analyzed by microarray and qPCR and sperm microRNA abundance by qPCR. Two subsequent generations were generated by mating F0 and then F1 mice to CD mice, and their metabolic health was investigated. All mice, other than F0 males, were maintained on a CD. HFD feeding induced paternal obesity with a 21% increase in adiposity, but not overt diabetes, and initiated intergenerational transmission of obesity and insulin resistance in two generations of offspring. This distinct phenotypic constellation is either partially or fully transmitted to both female and male F1 offspring and further transmitted through both parental lineages to the F2 generation, with a heightened effect on female F1 offspring (+67% in adiposity) and their F2 sons (+24% in adiposity). Founder male obesity altered the testes expression of 414 mRNAs by microarray and 11 microRNAs by qPCR, concomitant with alterations in sperm microRNA content and a 25% reduction in global methylation of germ cell DNA. Diet-induced paternal obesity modulates sperm microRNA content and germ cell methylation status, which are potential signals that program offspring health and initiate the transmission of obesity and impaired metabolic health to future generations. This study implicates paternal obesity in the transgenerational amplification of obesity and type 2 diabetes in humans.—Fullston, T., Ohlsson Teague, E. M. C., Palmer, N. O., DeBlasio, M. J., Mitchell, M., Corbett, M., Print, C. G., Owens, J. A., Lane, M. Paternal obesity initiates metabolic disturbances in two generations of mice with incomplete penetrance to the F2 generation and alters the transcriptional profile of testis and sperm microRNA content.en
dc.description.statementofresponsibilityTod Fullston, E. Maria C. Ohlsson Teague, Nicole O. Palmer, Miles J. DeBlasio, Megan Mitchell, Mark Corbett, Cristin G. Print, Julie A. Owens and Michelle Laneen
dc.language.isoenen
dc.publisherFederation Amer Soc Exp Biolen
dc.rights© 2013 FASEBen
dc.subjectnongenetic transmission; epigenetic alteration; methylation; DNA damage; ROSen
dc.titlePaternal obesity initiates metablic disturbances in two generations of mice with incomplete penetrance to the F₂ generation and alters the transcriptional profile of testis and sperm microRNA contenten
dc.title.alternativePaternal obesity initiates metablic disturbances in two generations of mice with incomplete penetrance to the F(2) generation and alters the transcriptional profile of testis and sperm microRNA contenten
dc.typeJournal articleen
dc.identifier.rmid0020131539en
dc.identifier.doi10.1096/fj.12-224048en
dc.identifier.pubid18135-
pubs.library.collectionObstetrics and Gynaecology publicationsen
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
dc.identifier.orcidFullston, T. [0000-0003-1314-3038]en
dc.identifier.orcidMc Pherson, N. [0000-0002-3492-9403]en
dc.identifier.orcidCorbett, M. [0000-0001-9298-3072]en
dc.identifier.orcidOwens, J. [0000-0002-7498-1353]en
Appears in Collections:Obstetrics and Gynaecology publications

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