Document Detail

Sex-dependent effect of a low neurosteroid environment and intrauterine growth restriction on fetal guinea pig brain development.
MedLine Citation:
PMID:  21149437     Owner:  NLM     Status:  Publisher    
Progesterone and its neuroactive metabolite, allopregnanolone, are present in high concentrations during pregnancy, but drop significantly following birth. Allopregnanolone influences fetal arousal and enhances cognitive and behavioural recovery following traumatic brain injury. Inhibition of allopregnanolone synthesis increases cell death in fetal animal brains with experimental hypoxia. We hypothesised that complications during pregnancy, such early or preterm loss of placental steroids and intra-uterine growth restriction (IUGR) would disrupt the fetal neurosteroid system, contributing to poor neurodevelopmental outcomes. The present study aimed to investigate the effects of chronic inhibition of allopregnanolone synthesis before term and IUGR on developmental processes in the fetal brain. Guinea pig fetuses were experimentally growth restricted at mid-gestation and treated with finasteride, an inhibitor of allopregnanolone synthesis. Finasteride treatment reduced fetal brain allopregnanolone concentrations by up to 75% and was associated with a reduction in MBP (P=0.001) and an increase in GFAP expression in the sub-cortical white matter brain region (P<0.001). IUGR resulted in decreased MBP expression (P<0.01) and was associated with a reduction in the expression of steroidogenic enzyme 5α-reductase (5αR) type 2 in the fetal brain (P=0.061). Brain levels of 5αR1 were higher in male fetuses (P=0.008). Both IUGR and reduced fetal brain concentrations of allopregnanolone were associated with altered expression of myelination and glial cell markers within the developing fetal brain. The potential role of neurosteroids in protecting and regulating neurodevelopmental processes in the fetal brain may provide new directions for treatment of neurodevelopmental disorders in infants that are exposed to perinatal insults and pathologies.
Meredith Anne Kelleher; Hannah Kate Palliser; David W Walker; Jonathan J Hirst
Related Documents :
21460147 - Effects of the maternal position and rest on the fetal urine production rate: a prospec...
21236247 - Cytokines in recurrent pregnancy loss.
16188377 - Endogenous selective inhibitors of 11beta-hydroxysteroid dehydrogenase isoforms 1 and 2...
21111487 - Seroconversion to islet autoantibodies between early pregnancy and delivery in non-diab...
1503537 - Clinical course of early fetal loss and its chromosomal characteristics.
6483787 - Creatine kinase estimation in pure fetal blood samples for the prenatal diagnosis of du...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2010-12-13
Journal Detail:
Title:  The Journal of endocrinology     Volume:  -     ISSN:  1479-6805     ISO Abbreviation:  -     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375363     Medline TA:  J Endocrinol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
M Kelleher, Mothers' & Babies Research Centre and School of Biomedical Sciences, University of Newcastle, Newcastle, Australia.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Effects of serving high-sugar cereals on children's breakfast-eating behavior.
Next Document:  Alleviation of hyperglycemia in diabetic rats by intraportal injection of insulin-producing cells ge...