A role for cellular senescence in birth timing

BackgroundSenescence is involved in many complications of pregnancy. However, whether senescent changes are also associated with missed miscarriage has not been fully investigated.MethodsThe levels of p16, p21, and γH2AX, markers of senescence, were measured in placentas collected from women with missed miscarriage by immunohistochemistry and Western blotting. Levels of misfolded proteins in missed miscarriage placentas or normal first-trimester placenta that had been treated with H2O2 (100 μM) or extracellular vesicles (EVs) collected from missed miscarriage placental explant culture were measured by fluorescent compound, thioflavin-T. The production of reactive oxygen species (ROS) by missed miscarriage placentas was measured by CellROX® Deep Red.ResultsIncreased levels of p16, p21, and γH2AX were presented in missed miscarriage placentas compared to controls. Increased levels of misfolded proteins were shown in missed miscarriage placentas, but not in EVs that were collected from missed miscarriage placentas. The ROS production was significantly increased in missed miscarriage placental explant cultures. Increased levels of misfolded proteins were seen in the normal first-trimester placenta that had been treated with H2O2 compared to untreated.ConclusionOur data demonstrate that there are increases in senescence and endoplasmic reticulum stress and ROS production in missed miscarriage placenta. Oxidative stress and an accumulation of misfolded proteins in missed miscarriage placentas may contribute to the changes of senescence and endoplasmic reticulum stress seen in missed miscarriage placentas.

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“…of p21, p16, and p19, loss of nuclear HMGB, and enhanced misfolded proteins [reviewed in Cha and Aronoff (2017)].…”

Section: Discussionmentioning

confidence: 99%

Senescent Changes and Endoplasmic Reticulum Stress May Be Involved in the Pathogenesis of Missed Miscarriage

Tang

Zhang

et al. 2021

Front. Cell Dev. Biol.

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“…A role for senescence in the timing of parturition has also been suggested (Cha and Aronoff, 2017;Menon et al, 2017). In pregnant mice with a conditional deletion of p53 in uterine tissues, half went into preterm labor (compared to none in controls) with increased markers of senescence including P21 CIP1 in post implantation decidual cells, i.e., cells of the pregnant endometrium that form the maternal placenta (Hirota et al, 2010).…”

Section: Physiological Roles Of Senescence Developmental Senescencementioning

confidence: 98%

Cellular Senescence and Senotherapies in the Kidney: Current Evidence and Future Directions

et al. 2020

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Cellular senescence refers to a cellular phenotype characterized by an altered transcriptome, pro-inflammatory secretome, and generally irreversible growth arrest. Acutely senescent cells are widely recognized as performing key physiological functions in vivo promoting normal organogenesis, successful wound repair, and cancer defense. In contrast, the accumulation of chronically senescent cells in response to aging, cell stress, genotoxic damage, and other injurious stimuli is increasingly recognized as an important contributor to organ dysfunction, tissue fibrosis, and the more generalized aging phenotype. In this review, we summarize our current knowledge of the role of senescent cells in promoting progressive fibrosis and dysfunction with a particular focus on the kidney and reference to other organ systems. Specific differences between healthy and senescent cells are reviewed along with a summary of several experimental pharmacological approaches to deplete or manipulate senescent cells to preserve organ integrity and function with aging and after injury. Finally, key questions for future research and clinical translation are discussed.

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“…Although these phenotypes have been characterized in detail in mouse embryos, developmental senescence has also been identified in human, chick, quail, axolotl, xenopus and zebra fish embryos (Nacher et al, 2006;Muñoz-Espín et al, 2013;Storer et al, 2013;Lorda-Diez et al, 2015;Davaapil et al, 2017;Villiard et al, 2017), indicating that it represents an evolutionary conserved mechanism. Interestingly, physiological senescence has also been observed in the placenta, where it has been associated to trophoblast cell fusion (Chuprin et al, 2013), as well as in embryonically-derived membranes, where its dysregulation could be related to pregnancy and parturition defects (Cha and Aronoff, 2017). From an evolutionary point of view, it appears that developmental senescence may represent a primitive form of senescence, directed to elicit cell-cycle arrest, cell clearance (Fig.…”

Section: Developmental Senescencementioning

confidence: 99%

Complementary and distinct roles of autophagy, apoptosis and senescence during early inner ear development

2019

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Auditory and vestibular organs form the adult vertebrate inner ear, both contain highly differentiated and specialized sensory epithelia that receive sound and position stimuli, respectively, and convey information to the brain (Magariños et al., 2012). Sensory patches of the inner ear contain sensory cells of two types, outer and inner hair cells, several types of supporting cells and neurons (Magariños et al., 2012; Burns et al., 2015). These cells do not regenerate in adult mammals, despite it has been described that there are small populations of resident stem cells in the adult inner ear (Oshima et al., 2007). Both sensory organs have a common developmental origin in the sensory otic placode, a thickening of the ectoderm that invaginates towards the neural tube forming the otic cup, which later closes up and forms the otic vesicle, also named otocyst (Adam et al., 1998; Magariños et al., 2012). The otic vesicle is an embryonic transitory organ that contains the information required to generate most cells of the adult inner ear (Magariños et al., 2014). The otic vesicle can be explanted and the whole organ cultured in Review Article Complementary and distinct roles of autophagy, apoptosis and senescence during early inner ear development

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A role for cellular senescence in birth timing

Cited by 29 publications

References 109 publications

Senescent Changes and Endoplasmic Reticulum Stress May Be Involved in the Pathogenesis of Missed Miscarriage

Senescent Changes and Endoplasmic Reticulum Stress May Be Involved in the Pathogenesis of Missed Miscarriage

Cellular Senescence and Senotherapies in the Kidney: Current Evidence and Future Directions

Complementary and distinct roles of autophagy, apoptosis and senescence during early inner ear development

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