Background: Cellular senescence is a state of metabolic and cell cycle arrest evoked by exogenous or endogenous stressors, especially genotoxic stress. Some cases of senescence are characterized by formation of senescence-associated heterochromatin foci (SAHF). Short, dysfunctional telomeres lead to senescence.

We have previously reported short telomeres in aneuploidy, intrauterine fetal growth restriction [IUGR].

We studied senescence in amniocytes and placentas from aneuploidic fetuses, in trophoblasts from IUGR fetuses, and from diabetic placentas, by assessing SAHF.

Methods: Using DAPI staining, we counted the percentage of cells with increased nuclear fragmentation (SAHF). We assessed SAHF expression in trophoblasts from placental biopsies (n=7) and in amniocytes (n=10) from known trisomy-21 fetuses and compared the results to control placentas (n=6) and to amniocytes (n=10) from fetuses with a known normal karyotype. We also assessed the presence of SAHF in trophoblasts from pregnancies complicated by IUGR (n=12) and from pregnancies complicated by uncontrolled diabetes mellitus [DM] (n=10) and compared them to gestational-age-matched controls from uncomplicated pregnancies (n=12).

Results: A significantly higher rate of cells with SAHF was found in trisomy-21 placentas and amniocytes, as well as in IUGR and in trophoblasts from pregnancies with uncontrolled diabetes compared to the control samples (Figure).

Conclusion: Increased SAHF formation in amniocytes and in trophoblasts that were previously found to express shorter telomeres emphasizes the correlation between short telomeres and senescence. These findings may be linked to other genetic instability parameters previously described in trisomy-21 and help explain intrauterine programming in pregnancies with IUGR and uncontrolled diabetes mellitus.

Authors:

Aliza Amiel ^_a,b, Moshe D. Fejgina^d,e, Meytal Liberman^a, Yehudit Sharon^b, Dvora Kidron^c, Tal Biron-Shental^d,e

aGenetics Institute, Meir Medical Center, Kfar Saba, Israel

bFaculty of Life Science, Bar Ilan University, Ramat Gan, Israel

cDepartment of Pathology, Meir Medical Center, Kfar Saba, Israel

dDepartment of OBGYN, Meir Medical Center, Kfar Saba, Israel

eSackler School of Medicine, Tel Aviv University, Tel Aviv, Israel