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Cited by 330Pregnancy and preeclampsia studiesNitric Oxide and Endothelin EffectsRedox biology and oxidative stress

Review: reactive oxygen and nitrogen species and functional adaptation of the placenta

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Myatt, L.·2010·Placenta
DOI 10.1016/j.placenta.2009.12.021PMC PMC2832707
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Abstract

The placenta regulates fetal growth and development via transport of nutrients and gases, and synthesis and secretion of steroid and peptide hormones. These functions are determined by vascular development and blood flow and by growth and differentiation of the trophoblast, which contains receptors, transporters and enzymes. The placenta generates reactive oxygen species which may contribute to the oxidative stress seen even in normal pregnancy but this is increased in pregnancies complicated by preeclampsia, IUGR and pregestational diabetes where oxidative and nitrative stress have been clearly documented. Nitrative stress is the covalent modification of proteins and DNA by peroxynitrite formed by the interaction of superoxide and nitric oxide. We have demonstrated nitrative stress by localizing nitrotyrosine residues in these placentas and found increased expression of NADPH oxidase (NOX) enzyme isoforms 1 and 5 as a potential source of superoxide generation. The presence of nitrative stress was associated with diminished vascular reactivity of the fetal placental circulation, a situation that could be reproduced by treatment with peroxynitrite in vitro. We find many nitrated proteins in the placenta, including p38 MAP kinase which has a role in development of the villous vasculature. Nitration of p38 MAPK was increased in the preeclamptic placenta and associated with loss of catalytic activity. We hypothesize that nitration of proteins in the placenta including receptors, transporters, enzymes and structural proteins can alter protein and placental function and this influences fetal growth and development. Increasing nitrative stress but a decrease in oxidative stress, measured as protein carbonylation, is found in the placenta with increasing BMI. Formation of peroxynitrite may then consume superoxide, decreasing nitrative stress. As protein carbonylation is a covalent modification at Lys, Arg, Pro and Thr residues the switch from carbonylation to nitration at tyrosine residues may alter protein function and hence placental function.

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  • Superoxide cannot diffuse beyond the cell of its origin due to its short half-life, whereas nitric oxide has a higher diffusion distance and can act as a paracrine mediator in adjacent cells and be potentially more damaging.

    “Superoxide is unable to diffuse across beyond the cell of its origin/synthesis because of short half life whereas the nitric oxide has a higher diffusion distance and can be a paracrine mediator in adjacent cells and be potentially more damaging (Myatt, 2010).”

    From Iron, Oxidative Stress and Health (2012) · cites this paper as Myatt, 2010

    Section 3, “Generation of oxidative and nitrative stress in the placenta” (page unavailable), says superoxide’s short diffusion distance limits it to the cell of synthesis, while nitric oxide can reach adjacent cells and act as a paracrine mediator. It does not say nitric oxide is potentially more damaging because it diffuses farther. Section 4 instead describes peroxynitrite, formed when nitric oxide reacts with superoxide, as a potent pro-oxidant. (LLM, conf=0.88)

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  • Gui et al. suggested that metformin reduced the rate of gestational hypertension because of its effects on endothelial function and its decrease in the production of reactive oxygen species.

    “Gui et al.(75) suggested that metformin reduced the rate of gestational hypertension because of its effects on endothelial function and its decrease in the production of reactive oxygen species, the two mechanisms implicated in the pathophysiology of preeclampsia(84–94).”

    From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [92]

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Authors
Myatt, L.
Affiliations
The University of Texas at San Antonio Health Science Center (US)
Corresponding author
Myatt, L.
ORCID
Myatt, L.
Venue
Placenta
Publisher
Elsevier BV
Published
2010-03
Volume
31
Pages
S66-S69
ISSN
0143-4004 (ISSN-L)
DOI
10.1016/j.placenta.2009.12.021
PMC
PMC2832707
OpenAlex
W2022536519
Cited by
330
References
53
Citations by year
2026: 10 · 2025: 13 · 2024: 13 · 2023: 15 · 2022: 20 · 2021: 20 · 2020: 15 · 2019: 21 · 2018: 12 · 2017: 22 · 2016: 17 · 2015: 30 · 2014: 29 · 2013: 27 · 2012: 27
FWCI
4.38
Type
journal article
Language
en
Open access
Licence
Locations
  • Placenta (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Heart, Lung, and Blood Institute (R01HL075297, R01HL057009)
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords
reactive oxygen species, reactive nitrogen species, oxidative stress, nitrative stress, peroxynitrite, nitrotyrosine, NADPH oxidase, p38 MAPK, protein nitration, protein carbonylation, preeclampsia, fetal growth restriction, pregestational diabetes, trophoblast, fetal growth
MeSH terms
Animals, Female, Humans, Maternal-Fetal Exchange, Oxidation-Reduction, Placenta, Pre-Eclampsia, Pregnancy, Reactive Oxygen Species, Oxidative Stress, Reactive Nitrogen Species

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