Document Detail

Trophoblast apoptosis from pregnancies complicated by fetal growth restriction is associated with enhanced p53 expression.
MedLine Citation:
PMID:  12015537     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: We tested the hypothesis that apoptotic trophoblasts from pregnancies associated with fetal growth restriction caused by preeclampsia or cigarette use exhibit enhanced expression of the proapoptotic proteins p53 and Bax and diminished expression of the antiapoptotic protein Bcl-2. STUDY DESIGN: Placentas were obtained from women with uncomplicated pregnancies (n = 4) or from women with pregnancies complicated by fetal growth restriction associated with preeclampsia, cigarette use, or both (n = 7). Placental sections were examined by means of hematoxylin and eosin and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining, as well as by detection of cytokeratin 18 cleavage products indicative of apoptosis. The expression of p53 was examined by means of Western immunoblotting and immunohistochemistry. The expression of Bax, Bcl-2, Bak, and Bcl-X(L) was analyzed by immunoblotting. RESULTS: More apoptosis was found in the trophoblast layer of villi from pregnancies complicated by fetal growth restriction than in the trophoblast layer of villi from control pregnancies. The enhanced apoptosis correlated with up-regulation of p53, primarily in cytotrophoblast nuclei. There was no difference between the two groups in expression of the proteins from the Bcl-2 family. CONCLUSIONS: The expression of p53, but not members of the Bcl-2 family of proteins is up-regulated in human placental villi from pregnancies complicated by fetal growth restriction. We speculate that conditions predisposing to placental hypoxia lead to p53-mediated apoptosis in trophoblasts and thereby contribute to placental dysfunction.
Roni Levy; Steven D Smith; Kamran Yusuf; Phyllis C Huettner; Frederick T Kraus; Yoel Sadovsky; D Michael Nelson
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of obstetrics and gynecology     Volume:  186     ISSN:  0002-9378     ISO Abbreviation:  Am. J. Obstet. Gynecol.     Publication Date:  2002 May 
Date Detail:
Created Date:  2002-05-16     Completed Date:  2002-06-13     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370476     Medline TA:  Am J Obstet Gynecol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1056-61     Citation Subset:  AIM; IM    
Department of Obstetrics and Gynecology, Washington University School of Medicine, St Louis, Mo 63110, USA.
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MeSH Terms
Chorionic Villi / physiopathology
Fetal Growth Retardation / physiopathology*
Pregnancy / physiology*
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-bcl-2 / metabolism
Reference Values
Trophoblasts / cytology,  physiology*
Tumor Suppressor Protein p53 / metabolism*
bcl-2-Associated X Protein
Grant Support
Reg. No./Substance:
0/BAX protein, human; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/Tumor Suppressor Protein p53; 0/bcl-2-Associated X Protein

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