Sensing senescence in preterm birth

Cincinnati Children's Research Foundation
Cell cycle (Georgetown, Tex.) (Impact Factor: 4.57). 01/2012; 11(2):205-6. DOI: 10.4161/cc.11.2.18781
Source: PubMed


Comment on: Hirota Y, et al. Proc Natl Acad Sci USA 2011; 108:18073-8.

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Available from: Jeeyeon Cha, Mar 15, 2014
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    • "The reports from Hirota et al. [27] and Burnum et al. [26] show molecular and histologic evidence of maternal decidual senescence as a trigger for PTB in animal model studies. The authors suggest that a functional p53 mutation (a prosenescence protein) in the decidua is associated with PTB [26] [27] [29]. Further analysis suggest that the reduction in the uterine antioxidant system is related to the mechanisms leading to PTB [30]. "
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    ABSTRACT: Many adverse pregnancy outcomes (APOs), including spontaneous preterm birth (PTB), are associated with placental dysfunction. Recent clinical and experimental evidences suggest that premature aging of the placenta may be involved in these events. Although placental aging is a well-known concept, the mechanisms of aging during normal pregnancy and premature aging in APOs are still unclear. This review was conducted to assess the knowledge on placental aging related biochemical changes leading to placental dysfunction in PTB and/or preterm premature rupture of membranes (pPROM). We performed a systematic review of studies published over the last 50 years in two electronic databases (Pubmed and Embase) on placental aging and PTB or pPROM. The search yielded 554 citations, 30 relevant studies were selected for full-text review and three were included in the review. Only one study reported oxidative stress-related aging and degenerative changes in human placental membranes and telomere length reduction in fetal cells as part of PTB and/or pPROM mechanisms. Similarly, two animal studies reported findings of decidual senescence and referred to PTB mechanisms. Placental and fetal membrane oxidative damage and telomere reduction are linked to premature aging in PTB and pPROM but the risk factors and biomolecular pathways causing this phenomenon are not established in the literature. However, no biomarkers or clinical indicators of premature aging as a pathology of PTB and pPROM have been reported. We document major knowledge gaps and propose several areas for future research to improve our understanding of premature aging linked to placental dysfunction. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Full-text · Article · May 2015 · Placenta
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    • "OS is a postulated etiology of spontaneous PTB and pPROM, although the precise mechanistic role of FR in these complications is unclear. Animal studies have shown that decidual senescence can lead to PTB by activating p53, a proapoptotic factor, and inflammatory cytokines [47, 48]. Recent biomolecular and histologic data on pPROM and PTB suggest that increased ROS and oxidative damage to lipids and DNA in fetoplacental cells play an important pathophysiological role in these disorders [49, 50]. "
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    ABSTRACT: Oxidative stress is worldwide recognized as a fundamental component of the aging, a process that begins before birth. There is a critical balance between free radical generation and antioxidant defenses. Oxidative stress is caused by an imbalance between the production of free radicals and the ability of antioxidant system to detoxify them. Oxidative stress can occur early in pregnancy and continue in the postnatal period; this damage is implicated in the pathophysiology of pregnancy-related disorders, including recurrent pregnancy loss, preeclampsia and preterm premature rupture of membranes. Moreover, diseases of the neonatal period such as bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and periventricular leukomalacia are related to free radical damage. The specific contribution of oxidative stress to the pathogenesis and progression of these neonatal diseases is only partially understood. This review summarizes what is known about the role of oxidative stress in pregnancy and in the pathogenesis of common disorders of the newborn, as a component of the early aging process.
    Full-text · Article · Aug 2014 · Oxidative Medicine and Cellular Longevity
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    • "This is especially true in early pPROM and PTB<34 weeks, where oxidative stress and pronounced inflammatory conditions are present. Animal studies have shown that decidual senescence can lead to PTB by activating p53 (a proapoptotic factor) and inflammatory cytokines [58], [59]. "
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    ABSTRACT: Oxidative stress is a postulated etiology of spontaneous preterm birth (PTB) and preterm prelabor rupture of the membranes (pPROM); however, the precise mechanistic role of reactive oxygen species (ROS) in these complications is unclear. The objective of this study is to examine impact of a water soluble cigarette smoke extract (wsCSE), a predicted cause of pregnancy complications, on human amnion epithelial cells. Amnion cells isolated from fetal membranes were exposed to wsCSE prepared in cell culture medium and changes in ROS levels, DNA base and strand damage was determined by using 2'7'-dichlorodihydro-fluorescein and comet assays as well as Fragment Length Analysis using Repair Enzymes (FLARE) assays, respectively. Western blot analyses were used to determine the changes in mass and post-translational modification of apoptosis signal-regulating kinase (ASK1), phospho-p38 (P-p38 MAPK), and p19(arf). Expression of senescence-associated β-galectosidase (SAβ-gal) was used to confirm cell ageing in situ. ROS levels in wsCSE-exposed amnion cells increased rapidly (within 2 min) and significantly (p<0.01) at all-time points, and DNA strand and base damage was evidenced by comet and FLARE assays. Activation of ASK1, P-p38 MAPK and p19(Arf) correlated with percentage of SAβ-gal expressing cells after wsCSE treatment. The antioxidant N-acetyl-L-cysteine (NAC) prevented ROS-induced DNA damage and phosphorylation of p38 MAPK, whereas activation of ASK1 and increased expression of p19(Arf) were not significantly affected by NAC. The findings support the hypothesis that compounds in wsCSE induces amnion cell senescence via a mechanism involving ROS and DNA damage. Both pathways may contribute to PTB and pPROM. Our results imply that antioxidant interventions that control ROS may interrupt pathways leading to pPROM and other causes of PTB.
    Full-text · Article · Dec 2013 · PLoS ONE
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