707: Mechanisms of telomere shortening in placentas from pregnancies complicated with intrauterine growth restriction

Abstract

Intrauterine Growth Restriction (IUGR) correlates with placental telomere shortening and senescence. Telomerase is an enzyme complex that elongates telomeres. Telomerase RNA component (TERC) gene serves as the RNA template for the addition of telomeric repeats. Telomerase reverse transctiptase (TERT) is the catalytic component of telomerase. We studies mechanisms of telomere shortening in IUGR placentas. We estimated the copy number of the TERC gene using FISH and the expression of TERT mRNA using RT-PCR, in placental biopsies from six pregnancies complicated with IUGR and from six gestational age matched controls. Lower TERC gene copy number was observed in IUGR trophoblasts (p<0.05). TERT mRNA was found to be diminished in IUGR placentas compared to control samples (mean fold of 0.5±0.2 and 0.96±0.1 respectively, p=0.0005). These results support and explain the observations of telomere shortening and decreased telomerase activity in IUGR placentas. We suggest that these findings may play a role in the pathophysiology of IUGR, perhaps by promoting senescence in trophoblasts of IUGR placentas.