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Placentas from pregnancies complicated with IUGR (intrauterine growth restriction) express altered telomere homeostasis. In the current study, we examined mechanisms of telomere shortening in these placentas.Placental biopsies from 15 IUGR and 15 healthy control pregnancies were examined. The percentage of trophoblasts with fragmented nuclei: senescence-associated heterochromatin foci (SAHF), was calculated using DAPI staining. The amount of human telomerase reverse transcriptase (hTERT) mRNA was evaluated using RtPCR levels of telomere capture using FISH in those samples were estimated.The percentage of trophoblasts with SAHF was higher in IUGR compared to control samples, (25±13.4% vs. 1.6±1.6%, P0.0001), hTERT mRNA was decreased (0.5±0.2 vs. 0.9±0.1, P0.0001) and telomere capture was increased (13.2±9.7% vs.1.3±2.5%, P0.001).We suggest that IUGR placentas express increased signs of senescence as part of the impaired telomere homeostasis. One factor that mediates telomere shortening in these placentas is decreased hTERT mRNA, leading to decreased protein expression and therefore, reduced telomere elongation. Telomere capture, which is a healing process, is increased in IUGR trophoblasts as a compensatory mechanism.

Objective Telomeres shorten and aggregate with cellular senescence and oxidative stress. Telomerase and its catalytic component human telomerase reverse-transcriptase regulate telomere length. The pathogenesis of preeclampsia and intrauterine growth restriction involves hypoxic stress. We aimed to assess telomere length in trophoblasts from pregnancies with those complications. Study Design Placental specimens from 4 groups of patients were studied: severe preeclampsia, intrauterine growth restriction, preeclampsia combined with intrauterine growth restriction, and uncomplicated (control). Telomere length and human telomerase reverse-transcriptase expression were assessed by using quantitative fluorescence-in-situ protocol and immunohistochemistry. Results Telomere length was significantly lower in preeclampsia, intrauterine growth restriction, and preeclampsia plus intrauterine growth restriction placentas. More aggregates were found in preeclampsia, but not in intrauterine growth restriction placentas. Human telomerase reverse-transcriptase was significantly higher in the controls compared with the other groups. Conclusion Telomeres are shorter in placentas from preeclampsia and intrauterine growth restriction pregnancies. Increased telomere aggregate formation in preeclampsia but not in intrauterine growth restriction pregnancies, implies different placental stress-related mechanisms in preeclampsia with or without intrauterine growth restriction.

pregnancies complicated with intrauterine growth restriction Tal Biron-Shental, Yudith Sharon, Dvora Kidron, Moshe D. Fejgin, Aliza Amiel Meir Medical Center, Tel Aviv University, Obstetrics and Gynecology, Kfar Saba, Israel, Meir Medical Center, Genetic Institute, Kfar Saba, Israel, Meir Medical Center, Tel Aviv University, Pathology, Kfar Saba, Israel, Meir Medical Center, Faculty of Life Sciences, Bar Ilan University, Genetic Institute, Kfar Saba, Israel 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. STUDY DESIGN: 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). CONCLUSION: 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.