Telomere shortening in intra uterine growth restriction placentas

Early Hum Dev. 2014 Sep;90(9):465-9. doi: 10.1016/j.earlhumdev.2014.06.003. Epub 2014 Jul 7.

Abstract

Introduction: 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.

Methods: 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.

Results: The percentage of trophoblasts with SAHF was higher in IUGR compared to control samples, (25±13.4% vs. 1.6±1.6%, P<0.0001), hTERT mRNA was decreased (0.5±0.2 vs. 0.9±0.1, P<0.0001) and telomere capture was increased (13.2±9.7% vs.1.3±2.5%, P<0.001).

Conclusions: 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.

Keywords: IUGR; Placenta; Senescence; Telomere; Telomere capture; Trophoblasts; hTERT.

MeSH terms

  • Case-Control Studies
  • Female
  • Fetal Growth Retardation / genetics*
  • Fetal Growth Retardation / pathology
  • Homeostasis
  • Humans
  • In Situ Hybridization, Fluorescence
  • Reverse Transcriptase Polymerase Chain Reaction
  • Telomere Shortening*