Treatment of the placenta prevents 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 whe...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| 格式: | Journal article |
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Nature Publishing Group
2017
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| _version_ | 1826281635963731968 |
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| author | Phillips, T Scott, H Menassa, D Bignell, A Sood, A Morton, J Akagi, T Azuma, K Rogers, M Gilmore, C Inman, G Grant, S Chung, Y Aljunaidy, M Cooke, C Steinkraus, B Pocklington, A Logan, A Collett, G Kemp, H Holmans, P Murphy, M Fulga, T Coney, A Akashi, M Davidge, S Case, C |
| author_facet | Phillips, T Scott, H Menassa, D Bignell, A Sood, A Morton, J Akagi, T Azuma, K Rogers, M Gilmore, C Inman, G Grant, S Chung, Y Aljunaidy, M Cooke, C Steinkraus, B Pocklington, A Logan, A Collett, G Kemp, H Holmans, P Murphy, M Fulga, T Coney, A Akashi, M Davidge, S Case, C |
| author_sort | Phillips, T |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T00:31:46Z |
| format | Journal article |
| id | oxford-uuid:800d116f-a31d-44fb-a98e-defc60d7d537 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T00:31:46Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:800d116f-a31d-44fb-a98e-defc60d7d5372022-03-26T21:20:55ZTreatment of the placenta prevents adverse effects of gestational hypoxia on fetal brain developmentJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:800d116f-a31d-44fb-a98e-defc60d7d537Symplectic Elements at OxfordNature Publishing Group2017Phillips, TScott, HMenassa, DBignell, ASood, AMorton, JAkagi, TAzuma, KRogers, MGilmore, CInman, GGrant, SChung, YAljunaidy, MCooke, CSteinkraus, BPocklington, ALogan, ACollett, GKemp, HHolmans, PMurphy, MFulga, TConey, AAkashi, MDavidge, SCase, CSome 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. |
| spellingShingle | Phillips, T Scott, H Menassa, D Bignell, A Sood, A Morton, J Akagi, T Azuma, K Rogers, M Gilmore, C Inman, G Grant, S Chung, Y Aljunaidy, M Cooke, C Steinkraus, B Pocklington, A Logan, A Collett, G Kemp, H Holmans, P Murphy, M Fulga, T Coney, A Akashi, M Davidge, S Case, C Treatment of the placenta prevents adverse effects of gestational hypoxia on fetal brain development |
| title | Treatment of the placenta prevents adverse effects of gestational hypoxia on fetal brain development |
| title_full | Treatment of the placenta prevents adverse effects of gestational hypoxia on fetal brain development |
| title_fullStr | Treatment of the placenta prevents adverse effects of gestational hypoxia on fetal brain development |
| title_full_unstemmed | Treatment of the placenta prevents adverse effects of gestational hypoxia on fetal brain development |
| title_short | Treatment of the placenta prevents adverse effects of gestational hypoxia on fetal brain development |
| title_sort | treatment of the placenta prevents adverse effects of gestational hypoxia on fetal brain development |
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