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Treating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development

Treating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development
Treating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development
Some neuropsychiatric disease, including schizophrenia, may originate during prenatal development, following periods of gestational hypoxia and placental oxidative stress. Here we investigated if gestational hypoxia promotes damaging secretions from the placenta that affect fetal development and whether a mitochondria-targeted antioxidant MitoQ might prevent this. Gestational hypoxia caused low birth-weight and changes in young adult offspring brain, mimicking those in human neuropsychiatric disease. Exposure of cultured neurons to fetal plasma or to secretions from the placenta or from model trophoblast barriers that had been exposed to altered oxygenation caused similar morphological changes. The secretions and plasma contained altered microRNAs whose targets were linked with changes in gene expression in the fetal brain and with human schizophrenia loci. Molecular and morphological changes in vivo and in vitro were prevented by a single dose of MitoQ bound to nanoparticles, which were shown to localise and prevent oxidative stress in the placenta but not in the fetus. We suggest the possibility of developing preventative treatments that target the placenta and not the fetus to reduce risk of psychiatric disease in later life.
2045-2322
1-16
Phillips, Tom J.
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Scott, Hannah
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Menassa, David A.
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Bignell, Ashleigh L.
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Sood, Aman
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Morton, Jude S.
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Akagi, Takami
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Azuma, Koki
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Rogers, Mark F.
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Gilmore, Catherine E.
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Inman, Gareth J.
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Grant, Simon
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Chung, Yealin
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Aljunaidy, Mais M.
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Cooke, Christy-lynn
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Steinkraus, Bruno R.
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Pocklington, Andrew
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Logan, Angela
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Collett, Gavin P.
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Kemp, Helena
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Holmans, Peter A.
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Murphy, Michael P.
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Fulga, Tudor A.
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Coney, Andrew M.
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Akashi, Mitsuru
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Davidge, Sandra T.
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Case, C. Patrick
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Phillips, Tom J.
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Scott, Hannah
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Menassa, David A.
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Bignell, Ashleigh L.
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Sood, Aman
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Morton, Jude S.
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Akagi, Takami
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Azuma, Koki
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Rogers, Mark F.
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Gilmore, Catherine E.
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Inman, Gareth J.
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Grant, Simon
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Chung, Yealin
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Aljunaidy, Mais M.
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Cooke, Christy-lynn
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Steinkraus, Bruno R.
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Pocklington, Andrew
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Logan, Angela
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Collett, Gavin P.
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Kemp, Helena
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Holmans, Peter A.
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Murphy, Michael P.
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Fulga, Tudor A.
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Coney, Andrew M.
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Akashi, Mitsuru
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Davidge, Sandra T.
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Case, C. Patrick
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Phillips, Tom J., Scott, Hannah, Menassa, David A., Bignell, Ashleigh L., Sood, Aman, Morton, Jude S., Akagi, Takami, Azuma, Koki, Rogers, Mark F., Gilmore, Catherine E., Inman, Gareth J., Grant, Simon, Chung, Yealin, Aljunaidy, Mais M., Cooke, Christy-lynn, Steinkraus, Bruno R., Pocklington, Andrew, Logan, Angela, Collett, Gavin P., Kemp, Helena, Holmans, Peter A., Murphy, Michael P., Fulga, Tudor A., Coney, Andrew M., Akashi, Mitsuru, Davidge, Sandra T. and Case, C. Patrick (2017) Treating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development. Scientific Reports, 7 (1), 1-16, [9079]. (doi:10.1038/s41598-017-06300-1).

Record type: Article

Abstract

Some neuropsychiatric disease, including schizophrenia, may originate during prenatal development, following periods of gestational hypoxia and placental oxidative stress. Here we investigated if gestational hypoxia promotes damaging secretions from the placenta that affect fetal development and whether a mitochondria-targeted antioxidant MitoQ might prevent this. Gestational hypoxia caused low birth-weight and changes in young adult offspring brain, mimicking those in human neuropsychiatric disease. Exposure of cultured neurons to fetal plasma or to secretions from the placenta or from model trophoblast barriers that had been exposed to altered oxygenation caused similar morphological changes. The secretions and plasma contained altered microRNAs whose targets were linked with changes in gene expression in the fetal brain and with human schizophrenia loci. Molecular and morphological changes in vivo and in vitro were prevented by a single dose of MitoQ bound to nanoparticles, which were shown to localise and prevent oxidative stress in the placenta but not in the fetus. We suggest the possibility of developing preventative treatments that target the placenta and not the fetus to reduce risk of psychiatric disease in later life.

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s41598-017-06300-1 - Version of Record
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Accepted/In Press date: 9 June 2017
e-pub ahead of print date: 22 August 2017

Identifiers

Local EPrints ID: 415026
URI: http://eprints.soton.ac.uk/id/eprint/415026
ISSN: 2045-2322
PURE UUID: de27ca44-020c-4f05-9aeb-010a5cb09075

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Date deposited: 21 Oct 2017 16:30
Last modified: 15 Mar 2024 16:32

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Contributors

Author: Tom J. Phillips
Author: Hannah Scott
Author: David A. Menassa
Author: Ashleigh L. Bignell
Author: Aman Sood
Author: Jude S. Morton
Author: Takami Akagi
Author: Koki Azuma
Author: Mark F. Rogers
Author: Catherine E. Gilmore
Author: Gareth J. Inman
Author: Simon Grant
Author: Yealin Chung
Author: Mais M. Aljunaidy
Author: Christy-lynn Cooke
Author: Bruno R. Steinkraus
Author: Andrew Pocklington
Author: Angela Logan
Author: Gavin P. Collett
Author: Helena Kemp
Author: Peter A. Holmans
Author: Michael P. Murphy
Author: Tudor A. Fulga
Author: Andrew M. Coney
Author: Mitsuru Akashi
Author: Sandra T. Davidge
Author: C. Patrick Case

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