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

Research output: Contribution to journalArticle

206 Citations (Scopus)

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.

Original languageEnglish (US)
JournalPlacenta
Volume31
Issue numberSUPPL.
DOIs
StatePublished - Mar 2010
Externally publishedYes

Fingerprint

Reactive Nitrogen Species
Placenta
Reactive Oxygen Species
Fetal Development
Peroxynitrous Acid
Protein Carbonylation
Superoxides
Oxidative Stress
p38 Mitogen-Activated Protein Kinases
Proteins
Growth and Development
Blood Vessels
Enzymes
Placental Circulation
Pregnancy Proteins
Pregnancy
Fetal Growth Retardation
Peptide Hormones
NADPH Oxidase
Trophoblasts

Keywords

  • Nitrative stress
  • Nitric oxide
  • Oxidative stress
  • Placenta
  • Superoxide

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Reproductive Medicine
  • Developmental Biology

Cite this

Review : Reactive oxygen and nitrogen species and functional adaptation of the placenta. / Myatt, Leslie.

In: Placenta, Vol. 31, No. SUPPL., 03.2010.

Research output: Contribution to journalArticle

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