Treating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development.
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Authors
Phillips, Tom J
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
Logan, Angela
Collett, Gavin P
Kemp, Helena
Holmans, Peter A
Fulga, Tudor A
Coney, Andrew M
Akashi, Mitsuru
Davidge, Sandra T
Case, C Patrick
Publication Date
2017-08-22Journal Title
Sci Rep
ISSN
2045-2322
Publisher
Springer Science and Business Media LLC
Volume
7
Issue
1
Pages
9079
Language
eng
Type
Article
This Version
VoR
Physical Medium
Electronic
Metadata
Show full item recordCitation
Phillips, T. J., Scott, H., Menassa, D. A., Bignell, A. L., Sood, A., Morton, J. S., Akagi, T., et al. (2017). Treating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development.. Sci Rep, 7 (1), 9079. https://doi.org/10.1038/s41598-017-06300-1
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.
Keywords
Brain, Fetus, Placenta, Animals, Rats, Pregnancy Complications, Reactive Oxygen Species, Antioxidants, Microscopy, Confocal, Gene Expression, Oxidative Stress, Fetal Development, Organogenesis, Pregnancy, Female, Biomarkers, Hypoxia
Sponsorship
Medical Research Council (MC_UU_00015/3)
Wellcome Trust (110159/Z/15/Z)
Medical Research Council (MC_U105663142)
Identifiers
External DOI: https://doi.org/10.1038/s41598-017-06300-1
This record's URL: https://www.repository.cam.ac.uk/handle/1810/277188
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