Short telomeres may play a role in placental dysfunction in preeclampsia and intrauterine growth restriction

Biron‐Shental, Tal; Sukenik-Halevy, Rivka; Sharon, Y. A. M. Villanueva; Goldberg‐Bittman, Lilach; Kidron, Dvora; Fejgin, Moshe D.; Amiel, Aliza

doi:10.1016/j.ajog.2010.01.036

Cited by 122 publications

(114 citation statements)

References 39 publications

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“…In particular, IL-6 has a central role in maintaining and amplifying the pro-senescence activity (Young and Narita 2009). Furthermore, APE1 also has a role in telomere maintenance that we saw to be involved in pregnancy diseases of placental origin (Madlener et al 2013;Biron-Shental et al 2010).…”

Section: Introductionmentioning

confidence: 78%

“…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%

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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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Section: Introductionmentioning

confidence: 78%

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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“…41 The absence of functional telomerase or loss of telomerase activity leads to progressive telomere shortening during cell division. 34,40 Telomere shortening may also be associated with a lack of adequate damage repair mechanisms that protect against DNA damage.…”

Section: Omerase Rna Component (Terc) Terc Is Widely Expressed Butmentioning

confidence: 99%

“…A significantly shorter telomere and/or an absent or reduced telomerase activity are observed in the placentas from IUGR pregnancies 41,88-90 with a reduced expression of hTERT, which is the rate-limiting factor in the telomerase activity. 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.…”

mentioning

confidence: 99%

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

Sultana

Maiti

Aitken

et al. 2017

American J Rep Immunol

218

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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“…On an organismal scale, short telomere syndromes exhibit strong correlations with certain pathologies, such as pulmonary fibrosis, 6,7 arteriosclerosis, 8 aplastic anemia, 6,9 chronic liver disease, 10 and intrauterine growth restriction (IUGR) due to trophoblast stem cell dysfunction. [11][12][13] Landmark work published by Carol Greider and Elizabeth Blackburn 14 uncovered the telomerase protein complex needed to re-lengthen telomeric DNA and maintain proliferation of a species and its germ cells. At the core of this ribonucleoprotein complex, the telomerase reverse transcriptase (TERT) protein in conjunction with its telomerase RNA component (TERC) is sufficient to extend telomeric sequences in vitro.…”

Section: Introductionmentioning

confidence: 99%

The role of telomeres and telomerase reverse transcriptase isoforms in pluripotency induction and maintenance

2016

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Telomeres are linear guanine-rich DNA structures at the ends of chromosomes. The length of telomeric DNA is actively regulated by a number of mechanisms in highly proliferative cells such as germ cells, cancer cells, and pluripotent stem cells. Telomeric DNA is synthesized by way of the ribonucleoprotein called telomerase containing a reverse transcriptase (TERT) subunit and RNA component (TERC). TERT is highly conserved across species and ubiquitously present in their respective pluripotent cells. Recent studies have uncovered intricate associations between telomeres and the self-renewal and differentiation properties of pluripotent stem cells. Interestingly, the past decade's work indicates that the TERT subunit also has the capacity to modulate mitochondrial function, to remodel chromatin structure, and to participate in key signaling pathways such as the Wnt/b-catenin pathway. Many of these non-canonical functions do not require TERT's catalytic activity, which hints at possible functions for the extensive number of alternatively spliced TERT isoforms that are highly expressed in pluripotent stem cells. In this review, some of the established and potential routes of pluripotency induction and maintenance are highlighted from the perspectives of telomere maintenance, known TERT isoform functions and their complex regulation.

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Short telomeres may play a role in placental dysfunction in preeclampsia and intrauterine growth restriction

Cited by 122 publications

References 39 publications

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

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

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

The role of telomeres and telomerase reverse transcriptase isoforms in pluripotency induction and maintenance

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