Telomere fragment induced amnion cell senescence: a contributor to parturition?

dc.contributor.authorPolettini, Jossimara [UNESP]
dc.contributor.authorBehnia, Faranak
dc.contributor.authorTaylor, Brandie D.
dc.contributor.authorSaade, George R.
dc.contributor.authorTaylor, Robert N.
dc.contributor.authorMenon, Ramkumar
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionThe University of Texas Medical Branch at Galveston
dc.contributor.institutionUniversity System Health Science Center
dc.contributor.institutionWake Forest University
dc.date.accessioned2015-12-07T15:31:36Z
dc.date.available2015-12-07T15:31:36Z
dc.date.issued2015
dc.description.abstractOxidative stress (OS)-induced senescence of the amniochorion has been associated with parturition at term. We investigated whether telomere fragments shed into the amniotic fluid (AF) correlated with labor status and tested if exogenous telomere fragments (T-oligos) could induce human and murine amnion cell senescence. In a cross-sectional clinical study, AF telomere fragment concentrations quantitated by a validated real-time PCR assay were higher in women in labor at term compared to those not in labor. In vitro treatment of primary human amnion epithelial cells with 40 μM T-oligos ([TTAGGG]2) that mimic telomere fragments, activated p38MAPK, produced senescence-associated (SA) β-gal staining and increased interleukin (IL)-6 and IL-8 production compared to cells treated with complementary DNA sequences (Cont-oligos, [AATCCC]2). T-oligos injected into the uteri of pregnant CD1 mice on day 14 of gestation, led to increased p38MAPK, SA-β-gal (SA β-gal) staining in murine amniotic sacs and higher AF IL-8 levels on day 18, compared to saline treated controls. In summary, term labor AF samples had higher telomere fragments than term not in labor AF. In vitro and in situ telomere fragments increased human and murine amnion p38MAPK, senescence and inflammatory cytokines. We propose that telomere fragments released from senescent fetal cells are indicative of fetal cell aging. Based on our data, these telomere fragments cause oxidative stress associated damages to the term amniotic sac and force them to release other DAMPS, which, in turn, provide a sterile immune response that may be one of the many inflammatory signals required to initiate parturition at term.en
dc.description.affiliationDivision of Maternal-Fetal Medicine and Perinatal Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States of America; Department of Pathology, Botucatu Medical School, UNESP-Univ. Estadual Paulista, Botucatu, Sao Paulo, Brazil.
dc.description.affiliationDivision of Maternal-Fetal Medicine and Perinatal Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States of America.
dc.description.affiliationDepartment of Epidemiology & Biostatistics, Texas A&M University System Health Science Center, College Station, Texas, United States of America.
dc.description.affiliationDepartment of Obstetrics and Gynecology, Wake Forest University, Winston Salem, North Carolina, United States of America.
dc.description.affiliationUnespDivision of Maternal-Fetal Medicine and Perinatal Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States of America; Department of Pathology, Botucatu Medical School, UNESP-Univ. Estadual Paulista, Botucatu, Sao Paulo, Brazil.
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.identifierhttp://dx.doi.org/10.1371/journal.pone.0137188
dc.identifier.citationPlos One, v. 10, n. 9, 2015.
dc.identifier.doi10.1371/journal.pone.0137188
dc.identifier.filePMC4580414.pdf
dc.identifier.issn1932-6203
dc.identifier.pmcPMC4580414
dc.identifier.pubmed26397719
dc.identifier.urihttp://hdl.handle.net/11449/131101
dc.language.isoeng
dc.publisherPublic Library Science
dc.relation.ispartofPlos One
dc.relation.ispartofjcr2.766
dc.relation.ispartofsjr1,164
dc.rights.accessRightsAcesso aberto
dc.sourcePubMed
dc.titleTelomere fragment induced amnion cell senescence: a contributor to parturition?en
dc.typeArtigo
dcterms.rightsHolderPublic Library Science
unesp.campusUniversidade Estadual Paulista (Unesp), Faculdade de Medicina, Botucatupt
unesp.departmentGinecologia e Obstetrícia - FMBpt

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