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

Autor: Phillips TJ; School of Clinical Sciences, University of Bristol, Southmead Hospital, Bristol, BS10 5NB, UK., Scott H; School of Clinical Sciences, University of Bristol, Southmead Hospital, Bristol, BS10 5NB, UK., Menassa DA; School of Clinical Sciences, University of Bristol, Southmead Hospital, Bristol, BS10 5NB, UK., Bignell AL; School of Clinical Sciences, University of Bristol, Southmead Hospital, Bristol, BS10 5NB, UK., Sood A; School of Clinical Sciences, University of Bristol, Southmead Hospital, Bristol, BS10 5NB, UK., Morton JS; Department of Obstetrics and Gynecology and Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada., Akagi T; Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Osaka, 565-0871, Japan.; Graduate School of Frontier Biosciences, Osaka University, Osaka, 565-0871, Japan., Azuma K; Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Osaka, 565-0871, Japan., Rogers MF; Intelligent Systems Laboratory, University of Bristol, Merchant Venturers Building, Bristol, BS8 1UB, UK., Gilmore CE; School of Clinical Sciences, University of Bristol, Southmead Hospital, Bristol, BS10 5NB, UK., Inman GJ; Division of Cancer Research, Jacqui Wood Cancer Centre, University of Dundee, Dundee, DD1 9SY, UK., Grant S; Department of Obstetrics, Southmead Hospital, Bristol, BS10 5NB, UK., Chung Y; School of Social and Community Medicine, University of Bristol, Southmead Hospital, Bristol, BS10 5NB, UK., Aljunaidy MM; Department of Obstetrics and Gynecology and Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada., Cooke CL; Department of Obstetrics and Gynecology and Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada., Steinkraus BR; Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, UK., Pocklington A; Institute of Psychological Medicine and Clinical Neurosciences and MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff, CF24 4HQ, UK., Logan A; MRC Mitochondrial Biology Unit, Wellcome Trust/MRC Building, Cambridge, CB2 0XY, UK., Collett GP; Nuffield Department of Obstetrics & Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK., Kemp H; Department of Clinical Biochemistry, Pathology Sciences Laboratory, Southmead Hospital, Bristol, BS10 5NB, UK., Holmans PA; Institute of Psychological Medicine and Clinical Neurosciences and MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff, CF24 4HQ, UK., Murphy MP; MRC Mitochondrial Biology Unit, Wellcome Trust/MRC Building, Cambridge, CB2 0XY, UK., Fulga TA; Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, UK., Coney AM; Institute of Clinical Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT, UK., Akashi M; Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Osaka, 565-0871, Japan.; Graduate School of Frontier Biosciences, Osaka University, Osaka, 565-0871, Japan., Davidge ST; Department of Obstetrics and Gynecology and Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada.; Department of Physiology, University of Alberta, Edmonton, Alberta, Canada., Case CP; School of Clinical Sciences, University of Bristol, Southmead Hospital, Bristol, BS10 5NB, UK. c.p.case@bristol.ac.uk.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2017 Aug 22; Vol. 7 (1), pp. 9079. Date of Electronic Publication: 2017 Aug 22.
DOI: 10.1038/s41598-017-06300-1
Abstrakt: 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.
Databáze: MEDLINE