317: Senescence and telomere shortening are enhanced in placentas from pregnancies with early compared to late onset preeclampsia

Abstract

Preeclampsia (PE) can appear early, prior to 34 weeks gestation or later during pregnancy. Both are placental pathologies however, the early onset (EOPE) tends to have more severe features compared to the late onset preeclampsia (LOPE). Impaired telomere homeostasis and senescence were previously shown as part of preeclampsia pathogenesis. In the current study we analyzed senescence and telomere characteristics in EOPE compared to LOPE. Placental biopsies from 7 early onset and 6 late onset preeclampsia (EOPE, LOPE) as well as 13 healthy gestational age-matched controls were examined. Clinical characteristics were compared. Telomere length and aggregate formation were assessed using qFISH and computer-assisted analysis methods. Senescence markers were evaluated, including Senescence-associated heterochromatin foci, β-galactosidase (SAβ-Gal) and P16 staining as was the expression of P16 cDNA using RT-qPCR. Maternal clinical characteristics were similar among both groups. EOPE fetuses were born earlier (34.1 ± 2.19 weeks Vs. 39.3 ± 0.816 weeks, P= 0.015) and had lower birth weights (2068 g ± 638 Vs. 3554 g ± 630; P =0.005) compared to LOPE fetuses. They also had a different mode of delivery- 6 out of 7 cases of EOPE were delivered by cesarean section as opposed to vaginal delivery in all LOPE and control cases. The percentage of trophoblasts with short telomeres was higher in placental samples from early onset (52.61±12.27%) vs. late onset PE (28.72±10.14%), both were higher relative to controls (7.53±5.14%, P=0.03). Aggregate formation was enhanced in early (8.72±2.49%) compared to late (4.54±1.45%) onset PE; both were higher than in healthy controls (2.72±1.08%, P=0.03). Trophoblasts from early vs. late onset PE were more likely to stain positive for SAβ-Gal and to P16 compared to controls (P<0.001). P16 cDNA expression assayed by RT-qPCR was 7.51 times higher in early onset PE than it was in controls, and 5.86 times higher than in late onset PE. Impaired telomere homeostasis and senescence markers are more prominent in early vs. late onset PE. These findings may contribute to our understanding of the pathophysiology of these entities and help explain their different clinical presentations.