Telomerase and Apoptosis in the Placental Trophoblasts of Growth Discordant Twins

Abstract

In an effort to investigate the molecular basis of growth discordance in embryos that experience the same uterine environment, we compared telomerase activity and apoptosis in placental trophoblasts obtained from growth discordant twins. Between January 2003 and February 2005, placental tissue from twenty pairs of twins was obtained within thirty minutes of delivery. Eleven cases were classified as growth discordant, with birth weight discordance greater than 20%. Nine cases comprised the control group, with less than 20% discordance. Telomerase and apoptotic activities in placental trophoblasts were analyzed by ELISA and immunoblot. Statistical significance was analyzed by a paired t-test, chisquared test, and ANOVA (SPSS ver 11.0). The average growth discordance was 26.8% in the growth discordant group and 14.4% in the control group. There were no significant differences in maternal age, week of gestation at delivery, parity, or chorionisity between the two groups. In the growth discordant group, the larger twin showed significantly higher telomerase activity ( p < 0.01), whereas no significant difference was observed in the control group ( p = 0.36). In addition, there was no definitive correlation between telomerase activity and the degree of growth discordance in the larger or smaller twins (R = -0.521 and -0.399, p = 0.15 and 0.25, respectively). The apoptosis proteins Bax and Bcl 2 were detected in both the larger and smaller twins in the growth discordant and control groups. There was no statistically significant difference in Bax expression between the larger and smaller twins ( p = 0.25 and 0.92, respectively) for either the growth discordant or the control groups. Bcl 2 expression also showed no significant difference between groups. In conclusion, a tendency toward reduced telomerase activity and increased apoptosis was discovered in placental trophoblasts of the smaller growth-discordant twin, possibility resulting in delayed fetal growth.

Maternal human telomerase reverse transcriptase variants are associated with preterm labor and preterm premature rupture of membranes

“…[ 46 – 47 ] A study of growth discordant twins showed a tendency toward reduced telomerase activity in placental trophoblasts of the smaller twin. [ 48 ] While the results are not consistent, they may suggest a link between altered telomerase expression and/or activity and premature aging of fetal tissue leading to placental insufficiency and growth restriction.…”

Is there a role for placental senescence in the genesis of obstetric complications and fetal growth restriction?

“…FGR placentas display senescence markers, including short telomeres, telomere aggregation or dysfunction, and a reduction of telomerase activity. 24,28,[94][95][96][97][98][99] Specifically a strong association between reduction of placental trophoblast telomere length and FGR pregnancies has been reported. 24,94,98-100 An absent or a decrease in telomerase activity is also observed in the placentas from FGR pregnancies.…”

Evaluation of cell proliferation and apoptosis in placentas of rats with severe diabetes

“…The apoptotic morphology includes loss of surface membrane specializations and cell anchorage concomitant with blebbing, chromatin condensation with nuclear fragmentation and cytoplasmic condensation with cell shrinkage (Levy and Nelson 2000). This event is energy-dependent and detected by terminal transferase-mediated in situ end labeling (TUNEL) (Kim et al 2006). Investigations with animal models have also shown that in streptozotocin-induced diabetic rats, placental growth is markedly altered, exhibiting a notable decrease in apoptotic and proliferation indexes (Rudge et al 2000).…”