Treating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development
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 developmen...
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Nature Portfolio
2017
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oai:doaj.org-article:b061c7fc2e2040a6b274efd65f22ba8a2021-12-02T15:06:01ZTreating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development10.1038/s41598-017-06300-12045-2322https://doaj.org/article/b061c7fc2e2040a6b274efd65f22ba8a2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06300-1https://doaj.org/toc/2045-2322Abstract 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.Tom J. PhillipsHannah ScottDavid A. MenassaAshleigh L. BignellAman SoodJude S. MortonTakami AkagiKoki AzumaMark F. RogersCatherine E. GilmoreGareth J. InmanSimon GrantYealin ChungMais M. AljunaidyChristy-Lynn CookeBruno R. SteinkrausAndrew PocklingtonAngela LoganGavin P. CollettHelena KempPeter A. HolmansMichael P. MurphyTudor A. FulgaAndrew M. ConeyMitsuru AkashiSandra T. DavidgeC. Patrick CaseNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017) |
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DOAJ |
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Medicine R Science Q |
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Medicine R Science Q Tom J. Phillips Hannah Scott David A. Menassa Ashleigh L. Bignell Aman Sood Jude S. Morton Takami Akagi Koki Azuma Mark F. Rogers Catherine E. Gilmore Gareth J. Inman Simon Grant Yealin Chung Mais M. Aljunaidy Christy-Lynn Cooke Bruno R. Steinkraus Andrew Pocklington Angela Logan Gavin P. Collett Helena Kemp Peter A. Holmans Michael P. Murphy Tudor A. Fulga Andrew M. Coney Mitsuru Akashi Sandra T. Davidge C. Patrick Case Treating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development |
| description |
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. |
| format |
article |
| author |
Tom J. Phillips Hannah Scott David A. Menassa Ashleigh L. Bignell Aman Sood Jude S. Morton Takami Akagi Koki Azuma Mark F. Rogers Catherine E. Gilmore Gareth J. Inman Simon Grant Yealin Chung Mais M. Aljunaidy Christy-Lynn Cooke Bruno R. Steinkraus Andrew Pocklington Angela Logan Gavin P. Collett Helena Kemp Peter A. Holmans Michael P. Murphy Tudor A. Fulga Andrew M. Coney Mitsuru Akashi Sandra T. Davidge C. Patrick Case |
| author_facet |
Tom J. Phillips Hannah Scott David A. Menassa Ashleigh L. Bignell Aman Sood Jude S. Morton Takami Akagi Koki Azuma Mark F. Rogers Catherine E. Gilmore Gareth J. Inman Simon Grant Yealin Chung Mais M. Aljunaidy Christy-Lynn Cooke Bruno R. Steinkraus Andrew Pocklington Angela Logan Gavin P. Collett Helena Kemp Peter A. Holmans Michael P. Murphy Tudor A. Fulga Andrew M. Coney Mitsuru Akashi Sandra T. Davidge C. Patrick Case |
| author_sort |
Tom J. Phillips |
| title |
Treating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development |
| title_short |
Treating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development |
| title_full |
Treating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development |
| title_fullStr |
Treating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development |
| title_full_unstemmed |
Treating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development |
| title_sort |
treating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/b061c7fc2e2040a6b274efd65f22ba8a |
| work_keys_str_mv |
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| _version_ |
1718388665180225536 |