Fetal Growth Restriction is Associated with Accelerated Telomere Shortening and Increased Expression of Cell Senescence Markers in the Placenta

Davy, Philip; Nagata, Melissa; Bullard, P.D.; Fogelson, Nicholas S.; Allsopp, Richard

doi:10.1016/j.placenta.2009.03.005

Cited by 120 publications

(89 citation statements)

References 18 publications

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“…This relationship between low birth weight and shorter TL has been found previously in placenta samples (Davy et al, 2009) but was not found in a small study measuring TL in cord blood (Akkad et al, 2006) nor in three cohorts (including 124 MZ and DZ twin pairs) from Finland (Kajantie et al, 2012). These negative reports do not necessarily contradict our findings.…”

Section: Discussionsupporting

confidence: 73%

Low Birth Weight in MZ Twins Discordant for Birth Weight is Associated with Shorter Telomere Length and lower IQ, but not Anxiety/Depression in Later Life

Strohmaier

Dongen²,

Willemsen³

et al. 2015

Twin Res Hum Genet

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Shorter telomere length (TL) has found to be associated with lower birth weight and with lower cognitive ability and psychiatric disorders. However, the direction of causation of these associations and the extent to which they are genetically or environmentally mediated are unclear. Within-pair comparisons of monozygotic (MZ) and dizygotic (DZ) twins can throw light on these questions. We investigated correlations of within pair differences in telomere length, IQ, and anxiety/depression in an initial sample from Brisbane (242 MZ pairs, 245 DZ same sex (DZSS) pairs) and in replication samples from Amsterdam (514 MZ pairs, 233 DZSS pairs) and Melbourne (19 pairs selected for extreme high or low birth weight difference). Intrapair differences of birth weight and telomere length were significantly correlated in MZ twins, but not in DZSS twins. Greater intra-pair differences of telomere length were observed in the 10% of MZ twins with the greatest difference in birth weight compared to the bottom 90% in both samples and also in the Melbourne sample. Intra-pair differences of telomere length and IQ, but not of TL and anxiety/depression, were correlated in MZ twins, and to a smaller extent in DZSS twins. Our findings suggest that the same prenatal effects that reduce birth weight also influence telomere length in MZ twins. The association between telomere length and IQ is partly driven by the same prenatal effects that decrease birth weight.

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Section: Discussionsupporting

confidence: 73%

Low Birth Weight in MZ Twins Discordant for Birth Weight is Associated with Shorter Telomere Length and lower IQ, but not Anxiety/Depression in Later Life

Strohmaier

Dongen²,

Willemsen³

et al. 2015

Twin Res Hum Genet

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“…41 Also, the expression of telomere-induced senescence markers p21 and p16 is elevated, and anti-apoptotic protein Bcl-2 is decreased in IUGR placentas. 88 Together with increased OS markers and reduced antioxidants capacity, the evidence of ageing markers supports the concept of the role of OS in placental ageing and IUGR.…”

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confidence: 59%

Oxidative stress, placental ageing‐related pathologies and adverse pregnancy outcomes

Sultana

Maiti

Aitken

et al. 2017

American J Rep Immunol

210

170

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Oxidative stress (OS), an imbalance between free radical generation and antioxidant defence, is recognized as a key factor in the pathogenesis of adverse pregnancy outcomes. Although OS is a common future of normal pregnancy, persistent, overwhelming OS leads to consumption and decline of antioxidants, affecting placental antioxidant capacity and reducing systems. The accumulation of OS causes damage to lipids, proteins and DNA in the placental tissue that induces a form of accelerated ageing.Premature ageing of the placenta is associated with placental insufficiency that prevents the organ meeting the needs of the foetus, and as a consequence, the viability of the foetus is compromised. This review summarizes the literature regarding the role of OS and premature placental ageing in the pathophysiology of pregnancy complications. K E Y W O R D Sintrauterine growth restriction, oxidative stress, placental ageing, pre-eclampsia, preterm birth, senescence, stillbirth | INTRODUCTIONAll living organisms have limited life cycles, and ageing is part of that life cycle. Each organ within an organism also exhibits ageing-related changes; the placenta is no exception. The placenta, a specialized organ formed during pregnancy, grows throughout gestation, performs multiple functions, including endocrine regulation and nourishment of the foetus, 1 but also ages and is discarded at the end of pregnancy, while the foetus may live for another hundred years. So placental ageing is a normal physiologic phenomenon. 2 However, there are likely to be some placentas which show signs of ageing earlier than others, in the same way as some individuals age more quickly than others. Premature ageing and degenerative changes in the placenta may reduce the functional capacity of the placenta and lead to abnormal pregnancy outcomes. The placenta is the primary organ for transferring nutrients from the mother to the foetus, so growth and function of the placenta are precisely regulated and coordinated to ensure the optimal growth and development of the foetus. The placenta exchanges nutrients, for example oxygen, amino acids, carbohydrates, minerals and waste products, for example carbon dioxide between the maternal and foetal circulatory systems. 3 It releases hormones into both the maternal and foetal circulations to affect uterine function, maternal metabolism, foetal growth and development. Moreover, it metabolizes some substances and can release metabolic products into both foetal and maternal circulations. The placenta can help to protect the foetus against certain xenobiotic molecules, infections and maternal diseases. Therefore, the adequate function of this organ is crucial for a normal physiologic gestational process and a healthy baby as a final outcome.In this review, we focus on the role of OS in the pathophysiology of pregnancy complications, beginning with a brief overview of placental development at different stages of gestation. We then discuss the biochemical markers of ageing and OS-induced placental ageing.Finally, we disc...

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“…The placenta is an organ that may be related to several diseases: preeclampsia (PE), HELLP syndrome (hemolysis, elevated liver enzymes, low platelet count), gestational hypertension (GH), intrauterine growth restriction (IUGR), and small for gestational age (SGA) fetus. In addition, recent studies suggest that cell senescence may play a role in PE and IUGR (Biron-Shental et al 2010;Kudo et al 2000;Izutsu et al 1998;Davy et al 2009). …”

Section: Introductionmentioning

confidence: 99%

Placental aging and oxidation damage in a tissue micro-array model: an immunohistochemistry study

Londero

Orsaria

Marzinotto

et al. 2016

Histochem Cell Biol

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To evaluate the expression of markers correlated with cellular senescence and DNA damage (8-hydroxy-2′-deoxy-guanosine (8-OHdG), p53, p21, APE1/Ref-1 (APE1), interleukin (IL-6 and IL-8) in placentas from healthy and pathologic pregnancies. This retrospective study considered a placental tissue micro-array containing 92 controls from different gestational ages and 158 pathological cases including preeclampsia (PE), HELLP syndrome (hemolysis, elevated liver enzymes,low platelet count), small for gestational age (SGA)fetuses, and intrauterine growth restriction (IUGR) occurringat different gestational ages. In this study, we demonstrated a significant influence of gestational age on the expression in the trophoblast of 8-OHdG, p53, p21, APE1, and IL-6. In placentas of cases affected by PE, HELLP, or IUGR, there was an increased expression of 8-OHdG, p53, APE1, and IL-6 compared to controls (only IL-8 was significantly decreased in cases). In both groups of pathology between 22- and 34-week gestation and after 34-week gestation, APE1 levels were higher in the trophoblast of women affected by hypertensive disorders of pregnancy than women carrying an IUGR fetus. The cytoplasmic expression of 8-OHdG was increased in placentas in IUGR cases compared to PE or HELLP pregnancies. In cases after 34-week gestation, p21 was higher in SGA and IUGR than in controls and late PE. Moreover, p53 was increased after 34-week gestation in IUGR pregnancies. Placentas from pathological pregnancies had an altered expression of\ud 8-OHdG, p53, p21, APE1, IL-6, and IL-8. The alterations of intracellular pathways involving these elements may be the cause or the consequence of placental dysfunction, but in any case reflect an impaired placental function, possibly due to increased aging velocity in pathologic cases

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Fetal Growth Restriction is Associated with Accelerated Telomere Shortening and Increased Expression of Cell Senescence Markers in the Placenta

Cited by 120 publications

References 18 publications

Low Birth Weight in MZ Twins Discordant for Birth Weight is Associated with Shorter Telomere Length and lower IQ, but not Anxiety/Depression in Later Life

Low Birth Weight in MZ Twins Discordant for Birth Weight is Associated with Shorter Telomere Length and lower IQ, but not Anxiety/Depression in Later Life

Oxidative stress, placental ageing‐related pathologies and adverse pregnancy outcomes

Placental aging and oxidation damage in a tissue micro-array model: an immunohistochemistry study

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