Document Detail


Thrombophilic-type placental pathologies and skeletal growth delay following maternal administration of angiostatin4.5 in mice.
MedLine Citation:
PMID:  20980690     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
During placentation, the concentration of fibrinous deposits on the surfaces of maternal vasculature plays a role in villous development and has been strongly implicated in the pathophysiology of human fetal growth restriction (FGR). Fibrinous deposits are conspicuous sites of platelet aggregation where there is local activation of the hemostatic cascade. During activation of the hemostatic cascade, a number of pro- and antiangiogenic agents may be generated at the cell surface, and an imbalance in these factors may contribute to the placental pathology characteristic of FGR. We tested the hypothesis that angiostatin(4.5) (AS(4.5)), a cleavage fragment of plasminogen liberated at the cell surface, is capable of causing FGR in mice. Increased maternal levels of AS(4.5) in vivo result in reproducible placental pathology, including an altered vascular compartment (both in decidual and labyrinthine layers) and increased apoptosis throughout the placenta. In addition, there is significant skeletal growth delay and conspicuous edema in fetuses from mothers that received AS(4.5). Maternally generated AS(4.5), therefore, can access maternal placental vasculature and have a severe effect on placental architecture and inhibit fetal development in vivo. These findings strongly support the hypothesis that maternal AS(4.5) levels can influence placental development, possibly by directly influencing trophoblast turnover in the placenta, and contribute to fetal growth delay in mice.
Authors:
Catrin S Rutland; Sarah D Atkinson; Mallinath Mukhopadhyay; Keyi Jiang; Gerald A Soff; Terry M Mayhew; Christopher A Mitchell
Publication Detail:
Type:  Journal Article     Date:  2010-10-27
Journal Detail:
Title:  Biology of reproduction     Volume:  84     ISSN:  1529-7268     ISO Abbreviation:  Biol. Reprod.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-02-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0207224     Medline TA:  Biol Reprod     Country:  United States    
Other Details:
Languages:  eng     Pagination:  505-13     Citation Subset:  IM    
Affiliation:
School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Leicestershire, United Kingdom.
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