title: Telomere homeostasis in trophoblasts and in cord blood cells from pregnancies complicated with preeclampsia.
abstract: BACKGROUND
  Telomeres are nucleoprotein structures, essential for chromosome stability and cell survival. Telomeres are progressively shortened with each cell division and by environmental factors. Telomere loss has been linked to age and stress-induced premature senescence. Dysfunctional telomeres tend to form aggregates, which consist of the end-to-end fusion of telomeres. Telomere elongation is carried out by telomerase, which is a specific reverse transcriptase capable of adding telomeric repeats to chromosome termini. The TERC gene encodes the RNA template of the telomerase. Another compensatory mechanism that is enhanced in response to telomere shortening and senescence is the telomere capture (TC). Telomere shortening and elevated aggregate formation have been observed in trophoblasts from pregnancies complicated with preeclampsia (PE).
  
  
  OBJECTIVE
  We opted to study mechanisms of telomere shortening in trophoblasts from pregnancies complicated with PE and to assess telomere length and homeostasis in fetal cord blood cells from PE pregnancies.
  
  
  METHODS
  Placental specimens and cord blood samples from uncomplicated pregnancies and from pregnancies complicated with PE were collected. Staining with 4',6-diamidino-2-phenylindole was used to assess nuclear fragmentation: senescence-associated heterochromatin foci (SAHF). Fluorescence in situ hybridization was used to evaluate TERC gene copy number and TC. Telomere length and aggregate formation were assessed in cord blood using quantitative fluorescence in situ hybridization. Nonparametric Kruskal-Wallis and Mann-Whitney U tests were applied to test the differences between the study groups.
  
  
  RESULTS
  Nine samples from pregnant patients with PE without intrauterine growth restriction and 14 samples from uncomplicated pregnancies that served as controls were collected. In cord blood cells, no differences were observed in telomere length, aggregate formation, TERC copy number, TC, or SAHF between PE and controls. In PE trophoblasts the percentage of cells with SAHF was higher in PE trophoblasts compared to controls (56.8 SD = 10.5% vs 35.2 SD = 10.7%, P = .028). The percentage of cells with abnormal TERC copy number was increased in PE trophoblasts compared to controls (31 ± 3.6% vs 12.97 SD = 5%, P = .004) as well as the percentage of cells with TC (27.4 SD = 9.4% vs 16 SD = 4.67%, P = .028).
  
  
  CONCLUSIONS
  We suggest that telomere shortening in PE 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 PE. The lack of telomere shortening, modified telomere homeostasis mechanisms, and increased senescence in cord blood from pregnancies complicated with PE suggests that these processes are probably restricted primarily to the placenta.
authors: Department of Obstetrics and Gynecology, Meir Medical Center, Kfar Saba, Israel; Genetics Institute, Meir Medical Center, Kfar Saba, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: Riki.sukenik@gmail.com.
authors: Rivka
authors: R
authors: Sukenik-Halevy
authors: Genetics Institute, Meir Medical Center, Kfar Saba, Israel; Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel.
authors: Aliza
authors: A
authors: Amiel
authors: Department of Pathology, Meir Medical Center, Kfar Saba, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Dvora
authors: D
authors: Kidron
authors: Genetics Institute, Meir Medical Center, Kfar Saba, Israel.
authors: Meital
authors: M
authors: Liberman
authors: Department of Obstetrics and Gynecology, Meir Medical Center, Kfar Saba, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Yael
authors: Y
authors: Ganor-Paz
authors: Department of Obstetrics and Gynecology, Meir Medical Center, Kfar Saba, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Tal
authors: T
authors: Biron-Shental
mesh_terms: D000328:Adult; D001773:Blood Cells / Q000378:metabolism*; D016022:Case-Control Studies; D016922:Cellular Senescence / Q000235:genetics*; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism*; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D010920:Placenta / Q000378:metabolism; D011225:Pre-Eclampsia / Q000235:genetics*; D011247:Pregnancy; D011446:Prospective Studies; D012313:RNA / Q000235:genetics*; D019098:Telomerase / Q000235:genetics*; D059505:Telomere Homeostasis / Q000235:genetics*; D059506:Telomere Shortening / Q000235:genetics*; D014327:Trophoblasts / Q000378:metabolism*; D055815:Young Adult
chemical_list: C422952:telomerase RNA; D012313:RNA; D019098:Telomerase
keywords: cord blood; preeclampsia; senescence; telomeres; trophoblasts