Telomere fragment induced amnion cell senescence

A contributor to parturition?

Jossimara Polettini, Faranak Behnia, Brandie D. Taylor, George Saade, Robert N. Taylor, Ramkumar Menon

    Research output: Contribution to journalArticle

    40 Citations (Scopus)

    Abstract

    Oxidative 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 μMT-oligos ([TTAGGG]2) thatmimic 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.

    Original languageEnglish (US)
    Article numbere0137188
    JournalPLoS One
    Volume10
    Issue number9
    DOIs
    StatePublished - Sep 23 2015

    Fingerprint

    amnion
    childbirth
    Amnion
    Cell Aging
    telomeres
    Telomere
    amniotic fluid
    Parturition
    Personnel
    Amniotic Fluid
    Fluids
    labor
    Oxidative stress
    Interleukin-8
    interleukin-8
    mice
    DNA sequences
    Oxidative Stress
    oxidative stress
    Staining and Labeling

    ASJC Scopus subject areas

    • Agricultural and Biological Sciences(all)
    • Biochemistry, Genetics and Molecular Biology(all)
    • Medicine(all)

    Cite this

    Telomere fragment induced amnion cell senescence : A contributor to parturition? / Polettini, Jossimara; Behnia, Faranak; Taylor, Brandie D.; Saade, George; Taylor, Robert N.; Menon, Ramkumar.

    In: PLoS One, Vol. 10, No. 9, e0137188, 23.09.2015.

    Research output: Contribution to journalArticle

    Polettini, Jossimara ; Behnia, Faranak ; Taylor, Brandie D. ; Saade, George ; Taylor, Robert N. ; Menon, Ramkumar. / Telomere fragment induced amnion cell senescence : A contributor to parturition?. In: PLoS One. 2015 ; Vol. 10, No. 9.
    @article{f93f8a33065046cc9b2362e5b95f3778,
    title = "Telomere fragment induced amnion cell senescence: A contributor to parturition?",
    abstract = "Oxidative 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 μMT-oligos ([TTAGGG]2) thatmimic 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.",
    author = "Jossimara Polettini and Faranak Behnia and Taylor, {Brandie D.} and George Saade and Taylor, {Robert N.} and Ramkumar Menon",
    year = "2015",
    month = "9",
    day = "23",
    doi = "10.1371/journal.pone.0137188",
    language = "English (US)",
    volume = "10",
    journal = "PLoS One",
    issn = "1932-6203",
    publisher = "Public Library of Science",
    number = "9",

    }

    TY - JOUR

    T1 - Telomere fragment induced amnion cell senescence

    T2 - A contributor to parturition?

    AU - Polettini, Jossimara

    AU - Behnia, Faranak

    AU - Taylor, Brandie D.

    AU - Saade, George

    AU - Taylor, Robert N.

    AU - Menon, Ramkumar

    PY - 2015/9/23

    Y1 - 2015/9/23

    N2 - Oxidative 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 μMT-oligos ([TTAGGG]2) thatmimic 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.

    AB - Oxidative 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 μMT-oligos ([TTAGGG]2) thatmimic 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.

    UR - http://www.scopus.com/inward/record.url?scp=84946934889&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=84946934889&partnerID=8YFLogxK

    U2 - 10.1371/journal.pone.0137188

    DO - 10.1371/journal.pone.0137188

    M3 - Article

    VL - 10

    JO - PLoS One

    JF - PLoS One

    SN - 1932-6203

    IS - 9

    M1 - e0137188

    ER -