Premature placental aging in term small-for-gestational-age and fetal-growth-restricted fetuses

Abstract

Objective The aim of this study was to perform a comprehensive assessment of the placental aging process through senescence and apoptotic markers in late-onset small fetuses classified as SGA or FGR. Study Design A prospective nested case-control study in singleton pregnancies delivering at term including 21 normally grown fetuses and 36 small fetuses classified into SGA (if birthweight was between the 3rd and 9th centile and normal fetoplacental Doppler; n=18) and FGR (if birthweight <3rd centile and/or abnormal cerebroplacental ratio or uterine artery Doppler; n=18). Telomerase activity, telomere length and RNA expression of senescence (Sirtuin 1,3,6) and apoptotic markers (p53, p21, BAX, Caspase 3 and 9) were analyzed in placental samples collected at birth. Results Compared with normally grown fetuses, both SGA and FGR presented signs of accelerated placental aging including lower telomerase activity (controls mean±SD 12.8% ± 6.6 vs SGA 7.98% ± 4.2 vs FGR 7.79% ± 4.6, p=0.008), shorter telomeres (controls 1.20 T/S ± 0.6 vs SGA 1.08 T/S ± 0.9 vs FGR 0.66 T/S ± 0.5, p=0.017), and reduced Sirtuin1 RNA expression (controls 1.55 2-' ' Ct ± 0.8 vs SGA 0.91 2-' ' Ct ± 0.8vs FGR 0.63 2-' ' Ct ± 0.5, p<0.001) together with increased p53 RNA expression (controls median(IQR) 1.072-' ' Ct (3.2) vs SGA 5.39 2-' ' Ct (15) vs FGR 3.75 2-' ' Ct (7.8), p=0.040), with a significant linear tendency across severity stages. In addition, FGR cases presented signs of apoptosis with increased RNA levels of Caspase 3 (controls 0.94 2-' ' Ct (1.1) vs FGR 3.98 2-' ' Ct (30), p=0.031) and Caspase 9 (controls 1.21 2-' ' Ct (4.0) vs FGR 3.87 2-' ' Ct (8.7), p=0.037) as compared to controls.