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Cited by 63Pregnancy and preeclampsia studiesGout, Hyperuricemia, Uric AcidAmino Acid Enzymes and Metabolism

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Uric Acid Inhibits Placental System A Amino Acid Uptake

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Bainbridge, S.A., von Versen-Höynck, F., Roberts, J.M.·2009·Placenta
DOI 10.1016/j.placenta.2008.10.015PMC PMC2677697
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Abstract

Hyperuricemia, a common clinical characteristic of preeclamptic pregnancies, has historically been considered a marker of reduced renal function in preeclamptic women. More recently it has been suggested that uric acid may directly contribute to pathological cell signaling events involved in disease progression as well as maternal and fetal pregnancy outcomes including fetal growth restriction. We hypothesize that the increased frequency of restricted fetal growth seen in relation to increasing uric acid concentrations in preeclamptic women is in part the result of uric acid-induced reductions in amino acid transport across the placenta. The objective of the current study was to examine the effects of uric acid on human placental System A amino acid transport using a primary placental villous explant model. Further, we examined the necessity of uric acid uptake and the role of redox signaling as a potential mechanism through which uric acid may attenuate System A activity. Placental uptake of a radiolabeled amino acid analogue, specific to the System A transporter, was reduced in a concentration-dependent fashion with increasing uric acid (0-7 mg/dL), corresponding to uric acid concentrations measured in healthy pregnant and preeclamptic women in the third trimester. Uric acid-induced reduction in System A activity was partially reversed by NADPH oxidase inhibition and completely eliminated by antioxidant treatment. This study demonstrates inhibition of placental System A amino acid transport with uric acid treatment, as a result of uric acid-induced stimulation of intracellular redox signaling cascades. These findings may be relevant to the increased frequency of fetal growth restriction observed in hyperuricemic preeclampsia. Additionally the results of this study, indicating a detrimental effect of hyperuricemia on amino acid transport in the placenta, at concentrations present in women with preeclampsia, also suggest a role for uric acid in the pathophysiology of preeclampsia.

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  • The explant model enabled the first demonstration of Zika virus infection of the first trimester placenta in vitro and has been used to investigate placental uptake of glucose, amino acids, and exosomes.

    “The explant model enabled the first demonstration of Zika virus infection of the first trimester placenta in vitro (144) and has been used to investigate placental uptake of other substances, including glucose (145), amino acids (146), and exosomes (147).”

    From Factors Affecting the FcRn-Mediated Transplacental Transfer of Antibodies and Implications for Vaccination in Pregnancy (2017) · cites this paper as [146]

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Metadata

Authors
Bainbridge, S. A., von Versen-Höynck, F., & Roberts, J. M.
Affiliations
University of Pittsburgh (US)
Corresponding author
Bainbridge, S.A.
ORCID
Venue
Placenta
Publisher
Elsevier BV
Published
2009-02
Volume
30
Issue
2
Pages
195-200
ISSN
0143-4004 (ISSN-L)
DOI
10.1016/j.placenta.2008.10.015
PMC
PMC2677697
OpenAlex
W2002977067
Cited by
63
References
0
Citations by year
2026: 4 · 2025: 2 · 2024: 6 · 2023: 7 · 2022: 4 · 2021: 3 · 2020: 1 · 2019: 4 · 2018: 4 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 6 · 2013: 5 · 2012: 4
FWCI
2.93
Type
journal article
Language
en
Open access
Licence
Locations
  • Placenta (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (UL1TR000005)
  • National Center for Advancing Translational Sciences
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01HD030367, P01 HD303967)
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
  • Health Sciences › Medicine › Nephrology › Gout, Hyperuricemia, Uric Acid
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Keywords
uric acid, hyperuricemia, preeclampsia, placental amino acid transport, fetal growth restriction, redox signaling, NADPH oxidase, placental villi, antioxidant treatment, placental function
MeSH terms
Acetophenones, Adult, Amino Acids, Antioxidants, Cell Survival, Chorionic Villi, Dose-Response Relationship, Drug, Enzyme Inhibitors, Female, Humans, Organ Culture Techniques, Pre-Eclampsia, Pregnancy, Pregnancy Trimester, Third, Uric Acid, Oxidative Stress, NADPH Oxidases, Amino Acid Transport System A, Young Adult

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