Differential senescence in feto-maternal tissues during mouse pregnancy

Bonney, Elizabeth A.; Krebs, Kendall; Saade, George R.; Kechichian, Talar; Trivedi, Jayshil; Yin, Huaizhi; Menon, Ramkumar

doi:10.1016/j.placenta.2016.04.018

Cited by 69 publications

(71 citation statements)

References 53 publications

(45 reference statements)

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“…These results were further supported by in vivo experiments, wherein injection of T-oligos into the uteri of pregnant CD1 mice on day 14 of gestation led to increased oxidative stress in the amniotic sac and placenta, increased MAPK14 activation and SA-β-gal activity in murine amniotic sac and higher IL8 levels in amniotic fluid compared with saline-treated controls (Polettini et al 2015b). These data indicate that telomere shortening can promote cellular senescence in fetal membranes and trigger an inflammatory cytokine signature to activate uterotonins and promote parturition at term, which is consistent with the idea that telomere shortening in fetal membranes can act as a biological clock to facilitate proper timing of parturition in humans and mice (Bonney et al 2016.…”

Section: :2supporting

confidence: 84%

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Positive and negative effects of cellular senescence during female reproductive aging and pregnancy

Velarde

Menon

2016

Journal of Endocrinology

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Cellular senescence is a phenomenon occurring when cells are no longer able to divide even after treatment with growth stimuli. Because senescent cells are typically associated with aging and age-related diseases, cellular senescence is hypothesized to contribute to the age-related decline in reproductive function. However, some data suggest that senescent cells may also be important for normal physiological functions during pregnancy. Herein, we review the positive and negative effects of cellular senescence on female reproductive aging and pregnancy. We discuss how senescent cells accelerate female reproductive aging by promoting the decline in the number of ovarian follicles and increasing complications during pregnancy. We also describe how cellular senescence plays an important role in placental and fetal development as a beneficial process, ensuring proper homeostasis during pregnancy.

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Section: :2supporting

confidence: 84%

“…In mouse fetal membranes, senescent cells also progressively increase throughout gestation and peaks at term (Bonney et al 2016), suggesting that cellular senescence in human and mouse fetal membranes may play a role in initiating parturition (Fig. 3).…”

Section: :2mentioning

confidence: 99%

Positive and negative effects of cellular senescence during female reproductive aging and pregnancy

Velarde

Menon

2016

Journal of Endocrinology

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“…In addition, women who underwent spontaneous labor at term have an elevated amniotic fluid concentration of senescence-associated secretory phenotype (SASP) markers [granulocytes macrophage colony-stimulating factor, interleukin (IL)-6 and IL-8] 33 , a greater number of telomere fragments in the amniotic fluid 34 , and a shorter telomere length and reduced lamin B1 in the chorioamnionitic membranes, as well as an upregulation of p21 35 , compared to those who delivered at term without labor. Further, in the murine chorioallantoic membranes, the telomere length shortens as the presence of mitogen-activated kinase p38 (p38-MAPK) 36 , active TP53, and SA-β-gal activity increases gradually throughout gestation 37 .…”

Section: Introductionmentioning

confidence: 99%

Preterm labor in the absence of acute histologic chorioamnionitis is characterized by cellular senescence of the chorioamniotic membranes

Gomez‐Lopez

Romero

Plazyo

et al. 2017

American Journal of Obstetrics and Gynecology

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Background Decidual senescence has been considered a mechanism of disease for spontaneous preterm labor in the absence of severe acute inflammation. Yet, signs of cellular senescence have also been observed in the chorioamniotic membranes from women who underwent the physiological process of labor at term. Objective We aimed to investigate whether, in the absence of acute histologic chorioamnionitis, the chorioamniotic membranes from women who underwent spontaneous preterm labor or labor at term exhibit markers of cellular senescence. Study Design Chorioamniotic membrane samples were collected from women who underwent spontaneous preterm labor or labor at term. Gestational age-matched non-labor controls were also included. Senescence-associated genes/proteins were determined using reverse transcription quantitative polymerase chain reaction analysis (n=7–9 each for array; n= 26–28 each for validation), enzyme-linked immunosorbent assays (n=7–9 each), immunoblotting (n=6–7 each) and immunohistochemistry (n=7–8 each). Senescence-associated β-galactosidase activity (n=7–11 each) and telomere length (n=15–22 each) were also evaluated. Results In the chorioamniotic membranes without acute histologic chorioamnionitis: 1) the expression profile of senescence-associated genes was different between the labor groups (term in labor and preterm in labor) and the non-labor groups (term no labor and preterm no labor); yet, there were differences between the term in labor and preterm in labor groups; 2) most of the differentially expressed genes among the groups were closely related to the tumor suppressor protein 53 (TP53) pathway; 3) the expression of TP53 was down-regulated in the term in labor and preterm in labor groups compared to their non-labor counterparts; 4) the expression of CDKN1A (gene coding for p21) was up-regulated in the term in labor and preterm in labor groups compared to their non-labor counterparts; 5) the expression of the cyclin kinase CDK2 and cyclins CCNA2, CCNB1 and CCNE1 was down-regulated in the preterm in labor group compared to the preterm no labor group; 6) the concentration of TP53 was lower in the preterm in labor group than in the preterm no labor and term in labor groups; 7) the senescence-associated β-galactosidase activity was greater in the preterm in labor group than in the preterm no labor and term in labor groups; 8) the concentration of phospho-S6 ribosomal protein was reduced in the term in labor group compared to its non-labor counterpart but no differences were observed between the preterm in labor and preterm no labor groups, and 9) no significant differences were observed in relative telomere length among the study groups (term no labor, term in labor, preterm no labor, and preterm in labor). Conclusion In the absence of acute histologic chorioamnionitis, signs of cellular senescence are present in the chorioamniotic membranes from women who underwent spontaneous preterm labor compared to those who delivered preterm in the absence of labor. However, the chorioamniotic me...

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“…35 It has also been suggested that labour is associated with senescence-associated changes in the placental membranes mediated by the p38 MAPK pathway, including telomere shortening, p38 MAPK activation and increased expression of p21 and SA-β-galactosidase. 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.…”

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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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Differential senescence in feto-maternal tissues during mouse pregnancy

Cited by 69 publications

References 53 publications

Positive and negative effects of cellular senescence during female reproductive aging and pregnancy

Positive and negative effects of cellular senescence during female reproductive aging and pregnancy

Preterm labor in the absence of acute histologic chorioamnionitis is characterized by cellular senescence of the chorioamniotic membranes

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

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