Histological Evidence of Oxidative Stress and Premature Senescence in Preterm Premature Rupture of the Human Fetal Membranes Recapitulated in Vitro

Menon, Ramkumar; Boldogh, István; Hawkins, Hal K.; Woodson, Michael; Syed, Tariq Ali; Fortunato, Stephen J.; Saade, George R.; Papaconstantinou, John; Taylor, Robert N.

doi:10.1016/j.ajpath.2014.02.011

Cited by 160 publications

(172 citation statements)

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“…Consistent with this idea, cellular senescence in fetal membranes is implicated in pregnancy complications, such as preterm premature rupture of the membranes (pPROM) (Menon et al 2014a). In relation to pregnancies with preterm birth without rupture of membranes (PTB with no ROM), pPROM pregnancies also have elevated amniotic fluid (AF) inflammatory markers (Athayde et al 1998(Athayde et al , 1999, high salivary collagenolytic activity (a surrogate for lower uterine segment activity) (Menon et al 2006), elevated AF F2-Isoprostane concentrations (a marker for oxidative stress) (Menon et al 2011a), shortened fetal leukocyte and placental DNA telomere length (a marker of cellular senescence) (Menon et al 2012), and distinct single nucleotide polymorphisms (SNPs) associated with common inflammatory pathway genes , Romero et al 2010a.…”

Section: :2mentioning

confidence: 67%

“…Endocrine signals like CRH alone are insufficient to produce changes in myometrium. Hence, we propose that premature telomere shortening in human fetal membranes may also trigger preterm labor or premature rupture of the membranes (Menon et al 2014a, Dutta et al 2016, providing an additional mechanism to induce parturition in humans.…”

Section: :2mentioning

confidence: 99%

“…3). Oxidative stress peaks at term and is thought to accelerate senescence of human fetal membranes (Menon et al 2014a). The third trimester of pregnancy is a state of hypoxic environment, but metabolism increases as fetal maturity is completed, enhancing the release of reactive oxygen species (ROS) (Diamant et al 1980, Many & Roberts 1997.…”

Section: :2mentioning

confidence: 99%

“…In addition, a gradual decrease in telomere length is also thought to promote the senescent phenotype in fetal membranes, as indicated by morphologic (enlargement of organelles) and biochemical alterations (activation of MAPK14, increase in SA-β-gal activity and development of the SASP) (Menon et al 2014a). This decrease in telomere length can be considered as a sign of replicative senescence, eventually resulting in the secretion of SASP factors, which are thought to initiate parturition during normal labor (Behnia et al 2015).…”

Section: :2mentioning

confidence: 99%

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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: :2mentioning

confidence: 67%

Section: :2mentioning

confidence: 99%

Section: :2mentioning

confidence: 99%

Section: :2mentioning

confidence: 99%

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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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“…Furthermore, polyunsaturated diacyl-PCs can promote the oxidation and fragmentation of γ-hydroxyalkenals [29]. Oxidative stress (OS) can occur early in pregnancy [30], induce pregnancy-related disorders like preeclampsia [31][32][33] and preterm premature rupture of membranes [34][35][36], and is considered a detrimental factor in preterm birth pathology [25]. Results of the current study showed that unsaturated diacyl-PCs (PCaaC36:4, PCaaC38:4, PCaaC38:5, PCaaC38:6, PCaaC40:4, PCaaC40:5, PCaaC40:6, PCaaC42:4), especially PCaaC38:6, were negatively correlated with gestational age.…”

Section: Discussionmentioning

confidence: 99%

Maternal PCaaC38:6 is Associated With Preterm Birth - a Risk Factor for Early and Late Adverse Outcome of the Offspring

Reichetzeder

et al. 2016

Kidney Blood Press Res

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Background/Aims: Preterm birth (PTB) and low birth weight (LBW) significantly influence mortality and morbidity of the offspring in early life and also have long-term consequences in later life. A better understanding of the molecular mechanisms of preterm birth could provide new insights regarding putative preventive strategies. Metabolomics provides a powerful analytic tool to readout complex interactions between genetics, environment and health and may serve to identify relevant biomarkers. In this study, the association between 163 targeted maternal blood metabolites and gestational age was investigated in order to find candidate biomarkers for PTB. Methods: Five hundred twenty-three women were included into this observational study. Maternal blood was obtained before delivery. The concentration of 163 maternal serum metabolites was measured by flow injection tandem mass spectrometry. To find putative biomarkers for preterm birth, a three-step analysis was designed: bivariate correlation analysis followed by multivariable regression analysis and a comparison of mean values among gestational age groups. Results: Bivariate correlation analysis showed that 2 acylcarnitines (C16:2, C2), 1 amino acids (xLeu), 8 diacyl-PCs (PCaaC36:4, PCaaC38:4, PCaaC38:5, PCaaC38:6, PCaaC40:4, PCaaC40:5, PCaaC40:6, PCaaC42:4), and 1 Acylalkyl-PCs (PCaeC40:5) were inversely correlated with gestational age. Multivariable regression analysis confounded for PTB history, maternal body mass index (BMI) before pregnancy, systolic blood pressure at the third trimester, and maternal body weight at the third trimester, showed that the diacyl-PC PCaaC38:6 was the only metabolite inversely correlated with gestational age. Conclusions: Maternal blood concentrations of PCaaC38:6 are independently associated with gestational age.

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Organ‐on‐a‐Chip Systems for Women's Health Applications

Nawroth

Rogal

Weiß

et al. 2017

Adv Healthcare Materials

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Biomedical research, for a long time, has paid little attention to the influence of sex in many areas of study, ranging from molecular and cellular biology to animal models and clinical studies on human subjects. Many studies solely rely on male cells/tissues/animals/humans, although there are profound differences in male and female physiology, which can significantly impact disease mechanisms, toxicity of compounds, and efficacy of pharmaceuticals. In vitro systems have been traditionally very limited in their capacity to recapitulate female-specific physiology and anatomy such as dynamic sex-hormone levels and the complex interdependencies of female reproductive tract organs. However, the advent of microphysiological organ-on-a-chip systems, which attempt to recreate the 3D structure and function of human organs, now gives researchers the opportunity to integrate cells and tissues from a variety of individuals. Moreover, adding a dynamic flow environment allows mimicking endocrine signaling during the menstrual cycle and pregnancy, as well as providing a controlled microfluidic environment for pharmacokinetic modeling. This review gives an introduction into preclinical and clinical research on women's health and discusses where organ-on-a-chip systems are already utilized or have the potential to deliver new insights and enable entirely new types of studies.

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Histological Evidence of Oxidative Stress and Premature Senescence in Preterm Premature Rupture of the Human Fetal Membranes Recapitulated in Vitro

Cited by 160 publications

References 62 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

Maternal PCaaC38:6 is Associated With Preterm Birth - a Risk Factor for Early and Late Adverse Outcome of the Offspring

Organ‐on‐a‐Chip Systems for Women's Health Applications

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