Intra-uterine growth restriction is associated with increased apoptosis and altered expression of proteins in the p53 pathway in villous trophoblast.
Intrauterine growth restriction (IUGR) affects 3-8% of pregnancies and is associated with altered cell turnover in the villous trophoblast, an essential functional cell type of the human placenta. The intrinsic pathway of apoptosis, particularly p53, is important in regulating placental cell turnover in response to damage. We hypothesised that expression of proteins in the p53 pathway in placental tissue would be altered in IUGR. Expression of constituents of the p53 pathway was assessed using real-time PCR, Western blotting and immunohistochemistry. p53 mRNA and protein expression was increased in IUGR, which localised to the syncytiotrophoblast. Similar changes were noted in p21 and Bax expression. There was no change in the expression of Mdm2, Bak and Bcl-2. The association between altered trophoblast cell turnover in IUGR and increased p53 expression is reminiscent of that following exposure to hypoxia. These observations provide further insight into the potential pathogenesis of IUGR. Further research is required to elicit the role and interactions of p53 and its place in the pathogenesis of IUGR.
Maternal and Fetal Health Research Group, St Mary's Hospital, University of Manchester, Hathersage Road, Manchester M13 0JH, UK. alex_heazell@talk21.com
Alexander E P
AE
Heazell
Andrew N
AN
Sharp
Philip N
PN
Baker
Ian P
IP
Crocker
D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D015153:Blotting, Western; D020169:Caspases / Q000235:genetics; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D015870:Gene Expression; D006801:Humans; D020287:In Situ Nick-End Labeling; D010920:Placenta / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D014327:Trophoblasts / Q000378:metabolism* / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000235:genetics; D054462:p21-Activated Kinases / Q000235:genetics
D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D054462:p21-Activated Kinases; D020169:Caspases