Keren Tzadikevitch-Geffen¹, Hilah Gal ², Valery Krizhanovsky², Ifat Vainer³, Aliza Amiel4, Tal Biron-Shental¹.
[1]Department of OBGYN, Meir Medical Center, Kfar Saba.
[2]Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot.
[3]Department of Pathology, Meir Medical Center, Kfar Saba.
[4] Genetics Institute, Meir Medical Center, Kfar Saba.
Introduction: Appropriate invasion of trophoblasts into the uterine wall is precisely regulated and essential for normal pregnancy development. Placenta accreta demonstrates an abnormality that might be a model for cancer research. Telomere dysfunction and cellular senescence have been implicated in tumor regulation. Therefore we opted to study telomere homeostasis and senescence expression in trophoblasts from placenta accreta.
Materials & Methods: Paraffin embedded placental biopsies from 10 cases of placenta accreta and 10 heathy controls were analyzed and compared. Telomere length and senescence associated heterochromatin foci (SAHF) were assessed using quantitative fluorescence-in-situ hybridization (Q-FISH). Cyclin dependent kinase inhibitors p21, p15, p16 and Tumor protein p53, known senescence related markers, were assessed using immunohistochemical staining.
Results: Shorter telomeres were significantly more common in trophoblasts from the placenta accreta samples compared to the healthy controls (52% Vs 2% ± 29SD, P<0.001). Less nucleic SAHF were revealed (10% Vs 36% ± 19SD, P=0.01), a higher expression of p15 (46.42% Vs 36.63% ± 14.4SD, P=0.002), a higher expression of p21 (59.8% Vs 47.5 % ± 22.7SD, P=0.007), and a lower expression of p16 (63.4% Vs 80.2% ± 16.79SD, P=0.0043) were demonstrated in the placenta accreta samples compared to the control samples. No difference was found in the expression of p53 (24.4% Vs 34 % ± 25.7SD, P=0.087) in the placenta accrete sample compared to the control.
Conclusion: Telomere homeostasis and senescence are differently expressed in placenta accreta. These changes might play a role in the pathophysiology of abnormal trophoblast invasion in placenta accreta.