title: Placental telomere shortening in stillbirth: a sign of premature senescence?
abstract: OBJECTIVE
  The objective of this study is to investigate placental telomere shortening in unexplained stillbirths (SBs) as an indication of premature senescence.
  
  
  METHODS
  Placentas were collected from 42 unexplained SB (>22 weeks), 43 term and 15 preterm live births, at the Policlinico Hospital of Modena (Italy). DNA extracted from placentae was studied for telomere length by real time PCR. Standard curves were generated for telomere lengths from single copy gene amplifications using a reference DNA. The telomere length for each sample was derived based on the ratio of telomere length between the sample and single copy gene standard (T/S ratio). The mean ratio of placental telomere in term live births was 5.181 ± 3.841.
  
  
  RESULTS
  A twofold decrease in telomere length was seen in SBs (over all 2.455 ± 1.239; p < 0.001). For early SBs (above 34 weeks), the T/S was 2.8884 ± 1.224 and for late SBs, the T/S was 2.207 ± 1.201, both lower than term live births (both p < 0.01). T/S remained lower both in small for gestational age-SB (2.639 ± 1.619) and appropriate for gestational age-SB (2.653 ± 1.335) with no difference between these subgroups (p = ns). T/S was lower in SB compared with spontaneous preterm births (PTBs) (6.382 ± 5.525; p < 0.01), whereas SBs telomere length were similar to those of preterm premature rupture of membranes (pPROM) (3.296 ± 3.599; p = ns).
  
  
  CONCLUSIONS
  Substantial reduction in telomere length in SBs is indicative of placental senescence. These data provide mechanistic insights that premature aging may lead to placental dysfunction as an initiator of fetal demise in unexplained SBs.
authors.affiliation: a Department of Obstetrics and Gynecology , Policlinico University Hospital of Modena, University of Modena and Reggio Emilia , Modena , MO , Italy and.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ferrari
authors.affiliation: a Department of Obstetrics and Gynecology , Policlinico University Hospital of Modena, University of Modena and Reggio Emilia , Modena , MO , Italy and.
authors.forename: Fabio
authors.initials: F
authors.lastname: Facchinetti
authors.affiliation: b Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine Perinatal Research , The University of Texas Medical Branch at Galveston , Galveston , TX , USA.
authors.forename: George
authors.initials: G
authors.lastname: Saade
authors.affiliation: b Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine Perinatal Research , The University of Texas Medical Branch at Galveston , Galveston , TX , USA.
authors.forename: Ramkumar
authors.initials: R
authors.lastname: Menon
mesh_terms: D000328:Adult; D000375:Aging / Q000473:pathology; D005260:Female; D005865:Gestational Age; D006801:Humans; D010920:Placenta / Q000473:pathology*; D010927:Placental Insufficiency / Q000473:pathology; D011247:Pregnancy; D047928:Premature Birth; D060888:Real-Time Polymerase Chain Reaction; D050497:Stillbirth / Q000235:genetics*; D059506:Telomere Shortening; D055815:Young Adult
keywords: Aging; oxidative stress; pPROM; preterm birth; risk factors; unexplained stillbirth