Intra-uterine growth restriction is associated with increased apoptosis and altered expression of proteins in the p53 pathway in villous trophoblast

Abstract

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.

Placental aging and oxidation damage in a tissue micro-array model: an immunohistochemistry study

“…This study provides a comparison between six placentas from normal pregnancies with a 39-week term and six placentas from IUGR pregnancies with a median of 37-week gestation (Heazell et al 2011). Here, Heazell and colleagues found an increased expression of p21 in IUGR when compared to controls (Heazell et al 2011). Our own results support these findings, indicating an increased expression of p21 in IUGR (and incidentally also in SGA pregnancies) compared to controls for patients who delivered after 34-week gestation.…”

“…This study provides a comparison between six placentas from normal pregnancies with a 39-week term and six placentas from IUGR pregnancies with a median of 37-week gestation (Heazell et al 2011). Here, Heazell and colleagues found an increased expression of p21 in IUGR when compared to controls (Heazell et al 2011).…”

“…Levy and colleagues and Heazell and colleagues showed an increase of p53 and of the cascade pro-apoptotic proteins in IUGR pregnancies compared to controls (Levy et al 2002;Heazell et al 2011). Contrary to these findings, Jeschke and colleagues evinced a reduced expression of p53 in cases of IUGR in relation to controls (Jeschke et al 2006), while Endo and colleagues found no difference in the expression of p53 between cases and controls (Endo et al 2005).…”

Sexual dimorphism in activation of placental autophagy in obese women with evidence for fetal programming from a placenta-specific mouse model

“…6C). Fetal growth restriction has been previously associated with overexpression of pro-apoptotic TRP53 (transformation related protein 53), 36,37 and activation of oxidative stress. 38 Western blot analyses show an increase in protein levels of TRP53 in placentas of KO Changes in placental morphology in placenta-specific Atg7 null mice Placentas of KO mice showed a 30% reduction in the area of the maternal decidua (29.3% § 0.8 in WT vs. 22.5% § 1.6 in KO, p D 0.02) and an 11% increase in the proportion occupied by the labyrinth zone responsible for maternal-fetal nutrient transfer (54.3% § 1.0 in WT vs. 59.8 § 0.8 in KO, p D 0.01; Fig.…”

Downregulation of p53 drives autophagy during human trophoblast differentiation

“…1e). While the expression of p53 has been investigated in placental samples [19,21,44] and in the context of trophoblast invasion [35,49], it has not been described as regulator in villous trophoblast differentiation. Besides being a prominent tumor suppressor in cancer cells, p53 is known to play a role in autophagy regulation [30].…”