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

Phillips, T. J. et al. (2017) Treating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development. Scientific Reports, 7, 9079. (doi: 10.1038/s41598-017-06300-1) (PMID:28831049) (PMCID:PMC5567270)

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.

• Item Type: Articles
• Additional Information: The authors acknowledge the very generous and valuable support of the Pervoli Trust. The work conducted in the Davidge laboratory is funded by grants from the Canadian Institutes of Health Research (CIHR); and the Women and Children’s Health Research Institute (WCHRI) through the generous contributions of the Stollery Children’s Hospital Foundation (SCHF) and the Royal Alexandra Hospital Foundation (RAHF). S. Davidge is a Canada Research Chair in Maternal and Perinatal Cardiovascular Health. Computing equipment was supported by an EPSRC grant (EP/K008250/1).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Inman, Professor Gareth
• Authors: Phillips, T. J., Scott, H., Menassa, D. A., Bignell, A. L., Sood, A., Morton, J. S., Akagi, T., Azuma, K., Rogers, M. F., Gilmore, C. E., Inman, G. J., Grant, S., Chung, Y., Aljunaidy, M. M., Cooke, C.-L., Steinkraus, B. R., Pocklington, A., Logan, A., Collett, G. P., Kemp, H., Holmans, P. A., Murphy, M. P., Fulga, T. A., Coney, A. M., Akashi, M., Davidge, S. T., and Case, C. P.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Scientific Reports
• Publisher: Nature Research
• ISSN: 2045-2322
• ISSN (Online): 2045-2322
• Copyright Holders: Copyright © 2017 The Authors
• First Published: First published in Scientific Reports 7:9079
• Publisher Policy: Reproduced under a Creative Commons License