Telomere Fragment Induced Amnion Cell Senescence: A Contributor to Parturition?

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

doi:10.1371/journal.pone.0137188

Cited by 77 publications

(101 citation statements)

References 85 publications

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“…These are released in response to senescent associated tissue damage. High mobility group box (HMGB) 1, cell free fetal cell DNA and telomere fragments, uric acid are some of the DAMPs that have been linked to parturition 113-115 . We postulate that at term, senescence causes increased inflammation due to tissue injury and this enhances the overall inflammatory load in feto-maternal tissues to initiate labor-associated changes.…”

Section: Novel Concepts In Pprommentioning

confidence: 99%

Preterm prelabor rupture of the membranes: A disease of the fetal membranes

Menon

Richardson

2017

Seminars in Perinatology

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202

178

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Preterm prelabor rupture of the membranes (pPROM) remains a significant obstetric problem that affects 3-4% of all pregnancies and precedes 40% to 50% of all preterm births. pPROM arises from complex, multifaceted pathways. In this review, we summarize some old concepts and introduce some novel theories related to pPROM pathophysiology. Specifically, we introduce the concept that pPROM is a disease of the fetal membranes where inflammation-oxidative stress axis plays a major role in producing pathways that can lead to membrane weakening through a variety of processes. In addition, we report microfractures in fetal membranes that are likely sites of tissue remodeling during gestation; however, increase in number and morphometry (width and depth) of these microfractures in pPROM membranes suggests reduced remodeling capacity of membranes. Microfractures can act as channels for amniotic fluid leak, and inflammatory cell and microbial migration. Further studies on senescence activation and microfracture formation and their role in maintaining membrane homeostasis are needed to fill the knowledge gaps in our understanding of pPROM as well as provide better screening (biomarker and imaging based) tools for predicting women at high risk for pPROM and subsequent preterm birth.

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Section: Novel Concepts In Pprommentioning

confidence: 99%

Preterm prelabor rupture of the membranes: A disease of the fetal membranes

Menon

Richardson

2017

Seminars in Perinatology

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202

178

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“…63 OS at term induces DNA damage and telomere shortening, which accelerates telomere-dependent senescence of the foetal membranes, resulting in senescence-associated inflammatory activation that may contribute to parturition. 64 It has long been thought both term and preterm labour have similar processes that occur through a "common pathway". The activation of this common pathway through physiologic signals results in term labour, while preterm labour is a "syndrome," which occurs from spontaneous activation of one or more of the components of the common pathway induced by multiple pathologic processes or risk factors.…”

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confidence: 99%

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

Sultana

Maiti

Aitken

et al. 2017

American J Rep Immunol

191

150

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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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“…A decreased level of autophagy is a characteristic of placentas evaluated following a vaginal delivery but is not a feature of placentas obtained by cesarean section from women who were not in labor (Signorelli et al 2011). Moreover, it was recently shown that oxidative stress at term is also associated with a decrease in chromosome telomere length and induced senescence of cells in the chorioamniotic membranes Polettini et al 2015). Senescence, an irreversible arrest of cell growth and subsequent cellular and/or tissue aging, is a process that occurs under both physiologic and pathologic conditions (Campisi and Robert 2014).…”

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confidence: 99%

The influence of oxidative stress and autophagy cross regulation on pregnancy outcome

Ramos

2016

Cell Stress and Chaperones

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The generation of reactive oxygen species (ROS), a byproduct of aerobic energy metabolism, is maintained at physiological levels by the activity of antioxidant components. Insufficiently opposed ROS results in oxidative stress characterized by altered mitochondrial function, decreased protein activity, damage to nucleic acids, and induction of apoptosis. Elevated levels of inadequately opposed ROS induce autophagy, a major intracellular pathway that sequesters and removes damaged macromolecules and organelles. In early pregnancy, autophagy induction preserves trophoblast function in the low oxygen and nutrient placental environment. Inadequate regulation of the ROS-autophagy axis leads to abnormal autophagy activity and contributes to the development of preeclampsia and intrauterine growth restriction. ROS-autophagy interactions are altered at the end of gestation and participate in the initiation of parturition at term. The induction of high levels of ROS coupled with a failure to induce a corresponding increase in autophagy results in the triggering of preterm labor and delivery.Keywords Oxidative stress . Autophagy . Preeclampsia . Intrauterine growth restriction . Preterm birth . PregnancyReactive oxygen species (ROS), such as superoxide radicals, hydroxyl radicals, alkoxy radicals as well as the non-radical intermediates hydrogen peroxide, ozone, and singlet oxygen, are byproducts of aerobic energy metabolism (Sies 1991;Finkel 2011). The concentration of these radicals is maintained at physiological levels by activity of the antioxidant enzymes superoxide dismutase, catalase, and peroxiredoxins as well as by concentrations of glutathione and vitamins C and E. When this system becomes out of balance, the generation of insufficiently opposed ROS results in altered mitochondrial function, a diminution of protein activity, damage to nucleic acids, and induction of apoptosis. The consequent tissue damage is manifested in a range of pathologies to different organ systems (Domingueti et al. 2015;Aluganti et al. 2016;Hernández et al. 2016). Recently, insufficiently regulated ROS has been recognized as a major contributor to disorders of pregnancy (Coppe et al. 2010;Redman and Sargent 2010;Menon 2014; Wu et al. 2015a, b;Zhang et al. 2015).A major pathway for removing macromolecules and organelles that have been damaged by ROS is macroautophagy, hereafter referred to as autophagy. This catabolic process is responsible for eliminating altered proteins, mitochondria, and inflammasomes from the cytoplasm. Macromolecules and organelles marked for destruction are enclosed within a doublemembrane structure called autophagosome. Its subsequent fusion with a lysosome results in degradation of the enclosed entity and release of the component amino acids, carbohydrates, nucleic acid degradation products, and lipids into the cytoplasm as building blocks for synthesis of new macromolecules or for the generation of energy by mitochondria. Autophagy is a constitutive process and functions at a low level under physiologica...

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Telomere Fragment Induced Amnion Cell Senescence: A Contributor to Parturition?

Cited by 77 publications

References 85 publications

Preterm prelabor rupture of the membranes: A disease of the fetal membranes

Preterm prelabor rupture of the membranes: A disease of the fetal membranes

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

The influence of oxidative stress and autophagy cross regulation on pregnancy outcome

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