Rivka Sukenik-Halevy,a,b,c Aliza Amiel b,d , Dvora Kidron c,e, Meital Libermanb ,
Yael Ganor-Paz a,c ,Tal Biron-Shental a,c
a Department of OBGYN, Meir Medical Center, Kfar Saba, Israel. b Genetic Institute, Meir Medical Center, Kfar Saba, Israel. c Sackler School of Medicine, Tel Aviv University, Tel Aviv, Kfar Saba, Israel. d Faculty of Life Science, Bar-Ilan University, Ramat Gan, Kfar Saba, Israel. e Department of Pathology, Meir Medical Center, Kfar Saba, Israel
Objective: Telomere shortening and elevated aggregate formation have been observed in throphoblasts from pregnancies complicated with Preeclampsia. In this study we opted to look into the mechanisms of telomere shortening in these cases as well as to assess telomere length and homeostasis in fetal cord blood.
Study Design: Placental specimens and cord blood from pregnancies complicated with preeclampsia and from uncomplicated pregnancies were collected. In throphoblases as well as in cord blood, the percentage of cells with fragmented nuclei: senescence-associated heterochromatin foci (SAHF), was calculated using DAPI staining. Florescence in situ hybridization (FISH) was used to assess the TERC gene copy number as well as the Telomere capture phenomenon (TC). Telomere length and aggregate formation was assessed in cord blood using quantitative FISH.
Results: In trophoblasts, the percentage of cells with SAHF was higher in PET compared to control samples, (56.8 ± 10.5% vs. 35.2± 10.7%, P = 0.028). The percentage of cells with abnormal TERC copy number was also increased in PET compared to controls, (28.48 ± 9.3% vs. 12.9± 15%, P = 0.006) as well as the percentage of cells with Telomere capture (27.4 ± 9.4% vs. 16± 4.67%, P = 0.028). In cord blood, no differences were observed in telomere length, aggregate formation, TERC copy number, TC or SAHF between PET and controls.
Conclusions: We suggest that telomere shortening in PET trophoblasts is linked to cellular increased senescence. Alterations in telomere homeostasis mechanisms are present in such cases. These findings support the role of telomeres in the pathogenesis of trophoblastic dysfunction in preeclampsia. The lack of telomere shortening, modified telomere homeostasis mechanisms and increased senescence in cord blood suggests that these processes are probably mainly located to the placenta.