Telomeres and replicative cellular aging of the human placenta and chorioamniotic membranes

Sci Rep. 2021 Mar 4;11(1):5115. doi: 10.1038/s41598-021-84728-2.

Abstract

Recent hypotheses propose that the human placenta and chorioamniotic membranes (CAMs) experience telomere length (TL)-mediated senescence. These hypotheses are based on mean TL (mTL) measurements, but replicative senescence is triggered by short and dysfunctional telomeres, not mTL. We measured short telomeres by a vanguard method, the Telomere shortest length assay, and telomere-dysfunction-induced DNA damage foci (TIF) in placentas and CAMs between 18-week gestation and at full-term. Both the placenta and CAMs showed a buildup of short telomeres and TIFs, but not shortening of mTL from 18-weeks to full-term. In the placenta, TIFs correlated with short telomeres but not mTL. CAMs of preterm birth pregnancies with intra-amniotic infection showed shorter mTL and increased proportions of short telomeres. We conclude that the placenta and probably the CAMs undergo TL-mediated replicative aging. Further research is warranted whether TL-mediated replicative aging plays a role in all preterm births.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aging / genetics
  • Cellular Senescence / genetics*
  • Chorioallantoic Membrane / growth & development
  • Chorioallantoic Membrane / metabolism*
  • DNA Damage / genetics
  • DNA Replication / genetics
  • Female
  • Gestational Age
  • Humans
  • In Situ Hybridization, Fluorescence
  • Infant, Newborn
  • Placenta / metabolism
  • Placenta / physiology*
  • Placentation
  • Pregnancy
  • Premature Birth / genetics
  • Premature Birth / pathology
  • Telomere / genetics
  • Telomere Homeostasis / genetics*