miR-30-5p-mediated ferroptosis of trophoblasts is implicated in the pathogenesis of preeclampsia

Zhang, Heng; He, Yue; Wang, Jianxia; Chen, Minghua; Xu, Jianjuan; Jiang, Minhui; Feng, Ying; Gu, Yanfang

doi:10.1016/j.redox.2019.101402

Cited by 139 publications

(84 citation statements)

References 38 publications

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“…In women with preeclampsia, increased iron and lipid ROS in the placenta coincide with ferroptosis in trophoblasts characterized by the downregulation of SLC7A11 and PAX3. 193 These findings suggest that inhibiting ferroptosis may be a potential strategy for treating reproductive toxicity caused by drugs or stress.…”

Section: Implications Of Ferroptosis In Diseasementioning

confidence: 98%

Ferroptosis: molecular mechanisms and health implications

et al. 2020

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Cell death can be executed through different subroutines. Since the description of ferroptosis as an iron-dependent form of non-apoptotic cell death in 2012, there has been mounting interest in the process and function of ferroptosis. Ferroptosis can occur through two major pathways, the extrinsic or transporter-dependent pathway and the intrinsic or enzyme-regulated pathway. Ferroptosis is caused by a redox imbalance between the production of oxidants and antioxidants, which is driven by the abnormal expression and activity of multiple redox-active enzymes that produce or detoxify free radicals and lipid oxidation products. Accordingly, ferroptosis is precisely regulated at multiple levels, including epigenetic, transcriptional, posttranscriptional and posttranslational layers. The transcription factor NFE2L2 plays a central role in upregulating anti-ferroptotic defense, whereas selective autophagy may promote ferroptotic death. Here, we review current knowledge on the integrated molecular machinery of ferroptosis and describe how dysregulated ferroptosis is involved in cancer, neurodegeneration, tissue injury, inflammation, and infection.

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Section: Implications Of Ferroptosis In Diseasementioning

confidence: 98%

Ferroptosis: molecular mechanisms and health implications

et al. 2020

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“…et al, 2018;Hirata et al, 2019), although oxytosis has long been considered to be the main mode leading to neuronal cell damage caused by glutamate toxicity (Tan et al, 2001). Inflammation mediated by ferroptotic cell death can promote pancreatitis (Liu et al, 2020d), liver fibrosis (Tsurusaki et al, 2019;Zeng et al, 2020), chronic obstructive pulmonary disease (COPD) (Park et al, 2019;Wang and Tang, 2019;Yoshida et al, 2019), inflammatory bowel disease (Mayr et al, 2020), and preeclampsia (Zhang et al, 2020). In addition, inhibiting ferroptosis can prevent I/R damage to various tissues, especially liver, kidney, brain, and heart (Linkermann et al, 2014;Skouta et al, 2014;Martin-Sanchez et al, 2017;Muller et al, 2017;Fang et al, 2019).…”

Section: Ferroptosis In Diseasementioning

confidence: 99%

Oxidative Damage and Antioxidant Defense in Ferroptosis

Kuang

Liu

Tang

et al. 2020

Front. Cell Dev. Biol.

272

145

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Many new types of regulated cell death have been recently implicated in human health and disease. These regulated cell deaths have different morphological, genetic, biochemical, and functional hallmarks. Ferroptosis was originally described as a carcinogenic RAS-dependent non-apoptotic cell death, and is now defined as a type of regulated necrosis characterized by iron accumulation, lipid peroxidation, and the release of damage-associated molecular patterns (DAMPs). Multiple oxidative and antioxidant systems, acting together autophagy machinery, shape the process of lipid peroxidation during ferroptosis. In particular, the production of reactive oxygen species (ROS) that depends on the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs) and the mitochondrial respiratory chain promotes lipid peroxidation by lipoxygenase (ALOX) or cytochrome P450 reductase (POR). In contrast, the glutathione (GSH), coenzyme Q10 (CoQ10), and tetrahydrobiopterin (BH 4) system limits oxidative damage during ferroptosis. These antioxidant processes are further transcriptionally regulated by nuclear factor, erythroid 2-like 2 (NFE2L2/NRF2), whereas membrane repair during ferroptotic damage requires the activation of endosomal sorting complexes required for transport (ESCRT)-III. A further understanding of the process and function of ferroptosis may provide precise treatment strategies for disease.

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“…Recently, Zhang and colleagues reported that oxidative stress-induced ferroptosis contributes to the pathogenesis of preeclampsia (72). Because decreased Gpx4, GSH, and SLC7A11 protein levels and increased MDA content are seen in the preeclamptic placenta in humans and rats (72), our findings together with this report support the notion that defective ferroptosis is involved in the pathophysiological processes of female reproductive disorders.…”

Section: Discussionmentioning

confidence: 99%

Induction of hyperandrogenism and insulin resistance differentially modulates ferroptosis in uterine and placental tissues of pregnant rats

Zhang

Jia

et al. 2020

Preprint

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Ferroptosis, a form of regulated necrotic cell death, plays roles in diverse physiological processes and diseases. Women with polycystic ovary syndrome (PCOS) have hyperandrogenism and insulin resistance (HAIR) and an increased risk of miscarriage and placental dysfunction during pregnancy. However, whether maternal HAIR alters mechanisms leading to ferroptosis in the gravid uterus and placenta remains unknown. Previous studies in rats showed that maternal exposure to 5α-dihydrotestosterone (DHT) and insulin (INS) from gestational day 7.5 to 13.5 induces HAIR and subsequently leads to placental insufficiency and fetal loss. We therefore hypothesized that maternal HAIR triggers ferroptosis in the uterus and placenta in association with fetal loss in pregnant rats. Compared with controls, we found that co-exposure to DHT and INS led to decreased levels of Gpx4 and glutathione (GSH), increased GSH+glutathione disulfide (GSSG) and malondialdehyde (MDA), aberrant expression of ferroptosis-associated genes (Acsl4, Tfrc, Slc7a11, and Gclc), increased iron deposition, and activated ERK/p38/JNK phosphorylation in the gravid uterus. However, in the placenta, DHT and INS exposure only partially altered the expression of ferroptosis-related markers (e.g., region-dependent Gpx4, GSH+GSSG, MDA, Gls2 and Slc7a11 mRNAs, and phosphorylated p38 levels). In the uteri co-exposed to DHT and INS, we also observed shrunken mitochondria with electron-dense cristae, which are key features of ferroptosis-related mitochondrial morphology, as well as increased expression of Dpp4, a mitochondria-encoded gene responsible for ferroptosis induction. In contrast, in placentas co-exposed to DHT and INS we found decreased expression of Dpp4 mRNA and increased expression of Cisd1 mRNA (a mitochondria-encoded iron-export factor). Further, DHT+INS-exposed pregnant rats exhibited decreased apoptosis in the uterus and increased necroptosis in the placenta. Our findings suggest that maternal HAIR causes the activation of ferroptosis in the gravid uterus and placenta, although this is mediated via different mechanisms operating at the molecular and cellular levels. Furthermore, our data suggest other cell death pathways may play a role in coordinating or compensating for HAIR-induced ferroptosis when the gravid uterus and placenta are dysfunctional.

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miR-30-5p-mediated ferroptosis of trophoblasts is implicated in the pathogenesis of preeclampsia

Cited by 139 publications

References 38 publications

Ferroptosis: molecular mechanisms and health implications

Ferroptosis: molecular mechanisms and health implications

Oxidative Damage and Antioxidant Defense in Ferroptosis

Induction of hyperandrogenism and insulin resistance differentially modulates ferroptosis in uterine and placental tissues of pregnant rats

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