Trophoblast apoptosis from pregnancies complicated by fetal growth restriction is associated with enhanced p53 expression.
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.


METHODS
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.
Levy
Roni
R
Department of Obstetrics and Gynecology, Washington University School of Medicine, St Louis, Mo 63110, USA.
Smith
Steven D
SD
Yusuf
Kamran
K
Huettner
Phyllis C
PC
Kraus
Frederick T
FT
Sadovsky
Yoel
Y
Nelson
D Michael
DM
D000328:Adult; D017209:Apoptosis; D002824:Chorionic Villi / Q000503:physiopathology; D005260:Female; D005317:Fetal Growth Retardation / Q000503:physiopathology*; D006801:Humans; D011247:Pregnancy / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012016:Reference Values; D014327:Trophoblasts / Q000166:cytology / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein