Objective: Telomeres are nucleoprotein structures sited at the termini of the chromosomes that protect them from end to end fusion and degradation. Intrauterine Growth Restriction (IUGR) correlates with placental telomere shortening and with senescence. Senescence is associated with changes in the nuclear chromatin known as senescence-associated heterochromatin foci (SAHFs). Shortened and therefore unstable chromosomes can be stabilized by transfer of telomeres from other chromosomes. This process is termed telomere capture. Our aim was to assess mechanisms of telomere shortening in placentas from pregnancies complicated with IUGR.
Methods: Placental biopsies derived from 13 pregnancies complicated with IUGR and from 12 gestational-age matched uncomplicated pregnancies. Clinical and histopathological characteristics were collected to ensure IUGR was secondary to placental insufficiency. We estimated the percentage of trophoblasts with SAHFs and the expression of the telomere capture mechanism using Dapi staining and FISH technique.
Results: Significantly increased expression of SAHFs (p=0.013) and significantly increased appearance of the telomere capture mechanism (p=0.023) were observed in placental biopsies from pregnancies complicated with IUGR compared to the control samples. (Table).
Conclusions: These results support and explain the observations of telomere shortening 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.
Tal Biron-Shentala,b, Yudith Sharonc,d, Dvora Kidronbe, Moshe D. Fejginab,c, Aliza Amielc,d
aDepartment of OBGYN department, Meir Medical Center, bSackler School of Medicine, Tel Aviv University, Tel Aviv, cGenetic Institute, Meir Hospital, Kfar-Saba, dFaculty of Life Science, Bar-Ilan University, Ramat Gan,eDeaprtment fo Pathology, Meir Hospital, Kfar-Saba.