The Potent Antioxidant MitoQ Protects Against Preeclampsia During Late Gestation but Increases the Risk of Preeclampsia When Administered in Early Pregnancy

Yang, Yong; Xu, Ping; Zhu, Fangyu; Liao, Jiujiang; Wu, Yue; Hu, Mingyu; Fu, Huijia; Qiao, Juan; Li, Lin; Huang, Biao; Jin, Huili; Liu, Xiyao; Zheng, Yaqiu; Li, Wen; Saffery, Richard; Kilby, Mark D.; Yan, Jianying; Kenny, Louise C.; Qi, Hongbo; Tong, Chao; Baker, Philip N.

doi:10.1089/ars.2019.7891

Cited by 44 publications

(37 citation statements)

References 63 publications

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“…However, mito-Tempo but not mitoQ improved litter size [73]. Similar reports have been provided by Yang et al showing the effectiveness of mitoQ in alleviating preeclampsia-like signs in a RUPP model established in mice [133]. Studies in vitro, have shown that mitoQ partially prevents the production of ROS from placental explants exposed to monoclonal antiphospholipid antibodies [134].…”

Section: Mito-tempo and Mitoqsupporting

confidence: 61%

Bioenergetics adaptations and redox homeostasis in pregnancy and related disorders

Sanchez-Aranguren

Nadeem

2021

Mol Cell Biochem

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Pregnancy is a challenging physiological process that involves maternal adaptations to the increasing energetics demands imposed by the growing conceptus. Failure to adapt to these requirements may result in serious health complications for the mother and the baby. The mitochondria are biosynthetic and energy-producing organelles supporting the augmented energetic demands of pregnancy. Evidence suggests that placental mitochondria display a dynamic phenotype through gestation. At early stages of pregnancy placental mitochondria are mainly responsible for the generation of metabolic intermediates and reactive oxygen species (ROS), while at later stages of gestation, the placental mitochondria exhibit high rates of oxygen consumption. This review describes the metabolic fingerprint of the placental mitochondria at different stages of pregnancy and summarises key signs of mitochondrial dysfunction in pathological pregnancy conditions, including preeclampsia, gestational diabetes and intrauterine growth restriction (IUGR). So far, the effects of placental-driven metabolic changes governing the metabolic adaptations occurring in different maternal tissues in both, healthy and pathological pregnancies, remain to be uncovered. Understanding the function and molecular aspects of the adaptations occurring in placental and maternal tissue’s mitochondria will unveil potential targets for further therapeutic exploration that could address pregnancy-related disorders. Targeting mitochondrial metabolism is an emerging approach for regulating mitochondrial bioenergetics. This review will also describe the potential therapeutic use of compounds with a recognised effect on mitochondria, for the management of preeclampsia.

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Section: Mito-tempo and Mitoqsupporting

confidence: 61%

Bioenergetics adaptations and redox homeostasis in pregnancy and related disorders

Sanchez-Aranguren

Nadeem

2021

Mol Cell Biochem

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“…Nevertheless, our findings show that impaired mRNA demethylation at the maternal-fetal interface due to low FTO levels can at least partly mediate SA pathogenesis. A dysfunctional placenta can significantly increase the risk of preeclampsia, fetal growth restriction (FGR) and early SA ( Rana et al, 2020 ; Yang et al, 2021 ). Based on our results, we recommend analysis of placental FTO demethylase levels in patients with late SA in order to determine whether these epigenetic changes are sudden or related to implantation.…”

Section: Discussionmentioning

confidence: 99%

RNA Demethylase FTO Mediated RNA m6A Modification Is Involved in Maintaining Maternal-Fetal Interface in Spontaneous Abortion

Qiu

Zhou

et al. 2021

Front. Cell Dev. Biol.

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The N6-methyladenosine (m6A) RNA modification regulates the expression of genes associated with various biological and pathological processes, including spontaneous abortion (SA). The aim of this study was to determine the role of the m6A demethylase fat mass and obesity (FTO)- associated protein in SA. The FTO,IGF2BP1 and IGF2BP2 mRNA levels were significantly lower in the chorionic villi obtained from spontaneously aborted pregnancies compared to that of normal pregnancies, while the expression levels of METTL3 and WTAP were significantly elevated. However, ALKBH5, YTHDF2, and IGF2BP3 were elevated with no statistical significance between groups. In addition, MDA was elevated and SOD levels were decreased in the villi tissues of the SA group compared to the normal group, which was indicative of placental oxidative stress in the former. Furthermore, the expression of FTO and HLA-G were significantly decreased in the trophoblasts of the SA patients compared to that of normal pregnant women, while that of m6A was markedly higher in the former. In addition, the HLA-G and VEGFR mRNA levels were downregulated in the SA versus the control group, and that of MMP2, MMP7, MMP9 and VEGFA were upregulated. Finally, The RIP assay showed significantly decreased levels of FTO-bound HLA-G, VEGFR and MMP9 RNA in SA patients (P < 0.05), which corresponded to an increase in transcripts enriched with the m6A antibody (P < 0.05). However, compared with normal pregnant women, the levels of HLA-G, VEGFA, VEGFR, and MMP2 mRNA bound by YTHDF2 were significantly decreased in SA patients. Compared to the normal pregnant women, both FTO- and m6A-bound MMP7 were significantly increased in SA patients (P < 0.05), but YTHDF2 almost unbound to MMP7 mRNA. In summary, the downregulation of FTO in the chorionic villi disrupts immune tolerance and angiogenesis at the maternal-fetal interface, resulting in aberrant methylation and oxidative stress that eventually leads to SA.

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“…Racial disparities tied to the placenta may have important implications for future therapeutics targeting improved placental growth and function during pregnancy. As pharmacologic therapies to reduce oxidant stress, 73,74 improve vascular growth and differentiation, 75,76 and ensure placental barrier protection and nutrient transfer 77 are explored, it will be important to understand whether racial disparities in the placenta exist that will positively or negatively influence response to these therapeutic agents. Lastly, nonpharmacologic approaches to reducing adverse pregnancy outcomes related to psychological stress may be particularly effective in combating the racial disparities of placental-mediated preterm birth.…”

Section: Research Gaps In Racial Disparities and Implications For Placental Therapeutics For Preterm Birthmentioning

confidence: 99%

Understanding Racial Disparities of Preterm Birth Through the Placenta

Matoba

Mestan

Collins

2021

Clinical Therapeutics

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The racial disparity associated with preterm birth is a public health concern in the United States. The placenta is the principal metabolic, respiratory, and endocrine organ of the fetus and a key route by which environmental exposures are transmitted from mother to offspring. Available at every delivery, it may serve as a marker of differences in prenatal exposures that manifest differently by race. Recently, we described differences in placental pathology between African-American and White preterm births: the prevalence of chronic inflammation was higher among African-American women's placentas compared with those of White women. Similarly, racial differences have been shown in placental malperfusion and placental weight. Social determinants such as poverty and stress from discrimination have been implicated in racial disparities in preterm birth. To date, however, the underlying biological mechanisms, whether through inflammatory, oxidative stress, or other pathways involving epigenetic programming, remain largely unknown. The placenta, complemented by maternal and umbilical cord blood biomarkers, may provide important information on the perinatal environment that explains the origins of racial disparities in preterm birth rates and subsequent health outcomes. This article reviews existing literature and current research gaps. Opportunities are discussed for future placental research that may reveal novel mechanisms leading to the development of new approaches in the prevention and management of preterm birth and its outcomes.

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The Potent Antioxidant MitoQ Protects Against Preeclampsia During Late Gestation but Increases the Risk of Preeclampsia When Administered in Early Pregnancy

Cited by 44 publications

References 63 publications

Bioenergetics adaptations and redox homeostasis in pregnancy and related disorders

Bioenergetics adaptations and redox homeostasis in pregnancy and related disorders

RNA Demethylase FTO Mediated RNA m6A Modification Is Involved in Maintaining Maternal-Fetal Interface in Spontaneous Abortion

Understanding Racial Disparities of Preterm Birth Through the Placenta

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