Oxidative Stress: Placenta Function and Dysfunction

Wu, Fan; Tian, Fu‐Ju; Lin, Yi; Xu, Wangming

doi:10.1111/aji.12454

Cited by 143 publications

(116 citation statements)

References 141 publications

(235 reference statements)

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confidence: 99%

“…1 Under normal conditions, oxidation and reduction factors are in a state of delicate balance, and ROS act as secondary messengers in trophoblast proliferation and differentiation. 1, 2 However, if there is an imbalance in the redox state, spontaneous abortion, preeclampsia or intrauterine growth restriction could occur. 1 Although ROS are necessary for cell growth signaling, high levels of ROS are associated with checkpoint responses that induce a transient or long-term pause in the cell cycle.…”

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Role of peroxiredoxin2 downregulation in recurrent miscarriage through regulation of trophoblast proliferation and apoptosis

Tian

Zeng

et al. 2017

Cell Death Dis

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Peroxiredoxin (Prdx) 2 is an antioxidant protein that utilizes its redox-sensitive cysteine groups to reduce hydrogen peroxide molecules and protect cells against oxidative damage from reactive oxygen species (ROS). However, its function in trophoblasts at the maternal–fetal interface has not been clarified yet. In this study, significantly lower Prdx2 expression was found in the first-trimester villous cytotrophoblasts of patients with recurrent miscarriage (RM) than in cytotrophoblasts from healthy controls. Further, Prdx2 knockdown inhibited proliferation and increased apoptosis of trophoblast cells. The reason for this may be an increase in the level of cellular ROS after knockdown of Prdx2, which may subsequently lead to an increase in the expression of phosphorylated p53 (p-p53) and p38-MAPK/p21. Prdx2 knockdown also impaired the fusion of BeWo cells induced by forskolin. Bioinformatics analysis identified a c-Myc-binding site in the Prdx2 promoter region, and chromatin immunoprecipitation verified that c-Myc directly bound to a site in this locus. Suppression and overexpression of c-Myc resulted in reduction and increase of Prdx2 expression respectively. Furthermore, we demonstrated that c-Myc was downregulated in the first-trimester cytotrophoblasts of patients with RM, and its downregulation is also related with inhibited cell proliferation, increased apoptosis, as well as upregulated p21 expression and p-p53/p53 ratio. Our findings indicate that Prdx2 might have an important role in the regulation of trophoblast proliferation and apoptosis during early pregnancy, and that its expression is mediated by c-Myc. Thus, these two proteins may be involved in the pathogenesis of RM and may represent potential therapeutic targets.

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confidence: 99%

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Role of peroxiredoxin2 downregulation in recurrent miscarriage through regulation of trophoblast proliferation and apoptosis

Tian

Zeng

et al. 2017

Cell Death Dis

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“…This oxidative imbalance induces NF-kB activation in the placenta and release of pro-inflammatory cytokines, chemokines, and anti-angiogenic factors such as soluble endoglin and soluble Fms-like tyrosine kinase-1 (sFLT-1) (Lazdam et al 2012). Increased levels of these compounds result in systemic inflammation and placental and endothelial damage resulting in the PEC phenotype Szarka et al 2010;Redman and Sargent 2010;Wu et al 2015b). As mentioned above, autophagy is also inhibited under these conditions.…”

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confidence: 99%

“…Placental insufficiency results in hypoxia/reoxygenation and synthesis of ROS leading to an inadequate nutrient supply to the growing fetus Wu et al 2015b). The degree of defective placentation may differentiate between cases of PEC-mediated IUGR from IUGR that occurs in the absence of concomitant hypertension (Myatt and Webster 2009).…”

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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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“…In addition, ROS could stimulate platelet adhesion and aggregation leading to intravascular coagulopathy with subsequent placental infarction and impairment of the uteroplacental blood flow (11) . OS also plays an important immuno-regulatory role during pregnancy (12) . Moreover, the balance between the protective and destructive mechanisms of placental autophagy and apoptosis are often influenced by OS, and the proper interactions between them play an important role in placental homeostasis (13) .…”

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confidence: 99%

Maternal Oxidant-Antioxidant Homeostasis During Normotensive and Preeclamptic Pregnancy.

MD¹,

MD²,

MD³

2018

IJAR

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Objectives: To evaluate changes in oxidant milieu in normotensive pregnant women (No PE) and those who developed pre-eclampsia (PE) and to define a relation between these changes and PE development. Patients & Methods: All pregnant women gave three blood samples at 12 th week (S1) gestational age, start of 3 rd trimester (S2) and 48-hr postpartum (S3) for spectrophotometeric estimation of serum levels of malondialdehyde (MDA) and uric acid (UA), and activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and catalase activity. Control group included a similar number of non-pregnant women. Blood pressures were estimated at 1 st visit and monthly for diagnosis of PE. Results: 65 pregnant women developed PE; 54 had mild and 11 had severe PE; while 19 women developed early and 46 late PE. Sample S1 levels showed non-significant differences between all study participants. S2 serum MDA levels were significantly higher in pregnant women than their S1 and control levels and in PE versus No PE women. S2 serum UA levels were significantly higher in PE women than their S1, control and corresponding levels in No PE women. S2 serum SOD and GPx activity was significantly lower in PE women than their S1, control and corresponding measures in No PE women. Serum GR and catalase activities were significantly lower in S2 samples of pregnant women than their S1 and control activities with significantly lower activity in No PE women. S3 serum levels of MDA and UA were decreased and activities of antioxidant enzymes were adjusted in S3 sample than in S2 sample, but with significant difference between PE and No PE women. Statistical analysis defined serum MDA at ≥13.2±0.128 µmole/L and GPx activity at ≥450 U/L as risk cutoff point for PE development. Conclusion: Pregnancy is stressful condition associated with activation of oxidative stress (OS) and overproduction of oxidative products and disturbed activity of antioxidant enzymes. Exaggerated OS compromises placental functions and induces development of hypertensive manifestations. Elevated serum MDA and GPx enzyme

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Oxidative Stress: Placenta Function and Dysfunction

Cited by 143 publications

References 141 publications

Role of peroxiredoxin2 downregulation in recurrent miscarriage through regulation of trophoblast proliferation and apoptosis

Role of peroxiredoxin2 downregulation in recurrent miscarriage through regulation of trophoblast proliferation and apoptosis

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

Maternal Oxidant-Antioxidant Homeostasis During Normotensive and Preeclamptic Pregnancy.

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