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Identification of Autophagic Vacuoles and Regulators of Autophagy in Villous Trophoblast from Normal Term Pregnancies and in Fetal Growth Restriction.
MedLine Citation:
PMID:  23039021     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Abstract Fetal growth restriction (FGR) is a serious pregnancy complication associated with increased perinatal mortality and morbidity. Although the majority of cases with FGR result from placental dysfunction, the pathophysiology is incompletely understood. Autophagy is a physiological form of cell degradation exacerbated by nutrient and oxygen restriction, which are both thought to play a role in the aetiology of FGR. We hypothesised that autophagy is present in the normal human placenta and is exaggerated in FGR. Autophagy was assessed in electron micrographs from normal and FGR placentas and by Western blotting for LC3B and LAMP-2. The localisation of regulators of autophagy was examined by immunohistochemistry. Culture of BeWo cells was used to investigate whether nutrient and/or oxygen deprivation can induce autophagy in trophoblast. Autophagy predominantly localised to the syncytiotrophoblast layer and autophagosomes were more frequent in FGR. The regulators LAMP-2, LC3B, Beclin-1, ATG 5, ATG9 and ATG16L1 were all present in villous trophoblast. LAMP-2 immunostaining was more punctate in FGR. In BeWo cells, culture in reduced oxygen tension and/or serum depleted conditions led to the appearance of autophagosomes which was associated with changes in LAMP-2 configuration. We conclude that autophagy in human term placenta may be involved in the placental dysfunction present in FGR.
Authors:
Sophie Curtis; Carolyn Jp Jones; Ainslie Garrod; Charlotte Hulme; Alexander Ep Heazell
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-8
Journal Detail:
Title:  The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians     Volume:  -     ISSN:  1476-4954     ISO Abbreviation:  J. Matern. Fetal. Neonatal. Med.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101136916     Medline TA:  J Matern Fetal Neonatal Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1Maternal and Fetal Health Research Centre, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, M13 9WL, UK.
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