Expression of Nuclear Factor-Kappa B and Placental Apoptosis in Pregnancies Complicated with Intrauterine Growth Restriction and Preeclampsia: An Immunohistochemical Study

Abstract

Preeclampsia affects 7-10% of all pregnancies, and is a major cause of maternal and fetal morbidity and mortality. Although enhanced apoptosis is well known in placentas with preeclampsia, the role of transcription factor nuclear factor-kappa B (NF-κ B) in the process is still being debated. In this work, we investigate the relationship between NF-κ B expression and trophoblastic cell apoptosis in pregnancies complicated with preeclampsia or intrauterine growth restriction (IUGR) by immunohistochemical analysis of NF-κ B and three apoptosis related markers: bcl-2, caspase-3, and M30 CytoDeath antibody that identifies early apoptotic changes in the cytoskeleton related to action of caspase. The study was conducted on placental samples from 19 preeclamptic, 5 IUGR-complicated and 10 normal pregnant women. The three conclusions from the statistical analysis of the data are obtained; (i) Significantly higher expression of NF-κ B in IUGR-complicated (p = 0.003) and preeclamptic placentas (p = 0.004) than the control placentas, (ii) significantly higher M30 index and caspase 3 expression in IUGR and preeclampsia placentas (p = 0.003), and (iii) decreased expression of bcl-2 in IUGR and preeclampsia placentas (p = 0.001). Based on these observations, we suggest that increased trophoblastic apoptosis is at least partially induced by NF-κ B and reduced bcl-2 expression. preeclampsia; IUGR; apoptosis; NF-κ B; bcl-2

Effect of high oxygen on placental function in short-term explant cultures

“…Similarly at both 95% and 21% oxygen, but not at 8% oxygen, M30 staining increased between the incubation time points of 6 h and 24 h. M30 antibody, as an apoptotic detection marker, has proven to be superior to the TUNEL method for the detection of apoptosis in villous and extravillous trophoblast (Kadyrov et al 2001). These findings are supported by those previously described in placentae recovered from pregnancies complicated by preeclampsia, which is associated with a significantly higher M30 index than that measured in control placentas (Aban et al 2004;Lee et al 2005). Thus, in summary, hyperoxic conditions have been shown significantly to increase apoptosis in human term placental explants in vitro.…”

Maternal Hypothyroidism and Its Rolein the Placenta: A Morphometric andImmunohistochemical Study

“…These findings agreed with those of Aban et al who researched complicated pregnancies. 26 Bax immunoreactivity was negative in cytotrophoblasts and mesenchymal cells and was mild in syncytiotrophoblasts in the control group; whereas moderate response was observed cytototrophoblasts and syncytiotrophoblasts and mild response in mesenchymal cells in hypothyroid placentas. These findings correlate with findings of Cobellis et al who investigated apoptosis in growth retardation as a consequence of pre-eclampsia.…”

“…Caspase-3 is involved in the development of apoptotic cell death. [21][22][23][24][25][26] An abnormal level of apoptosis has also been correlated with a large variety of gestational pathologies such as in the placentas of abortions, ectopic pregnancy, intrauterine growth retardation, post-term pregnancy, pre-eclampsia and maternal hypertension syndrome. 17,[27][28][29] Apoptosis has occasionally been observed in histological sections of normal thyroid.…”

Environmental factors and apoptotic indices in patients with intrauterine growth retardation: A nested case-control study

“…The diagnosis of IUGR was based on three criteria: ultrasonographic deviation from the normal growth percentile, clinically detected suboptimal growth and having birth weight less than the 10th percentile of the corresponding gestational age (Aban et al, 2004).…”