Telomere length predicts embryo fragmentation after in vitro fertilization in women - Toward a telomere theory of reproductive aging in women

David L. Keefe, Sonia Franco, Lin Liu, James Trimarchi, Benning Cao, Sherry Weitzen, Shoba Agarwal, Maria A. Blasco

Research output: Contribution to journalArticle

Abstract

Objective: Telomeres are DNA repeats which cap and protect chromosome ends, facilitate homologue pairing and chiasmata formation during early meiosis, and shorten with cell division and exposure to reactive oxygen to mediate aging. Early germ cells contain telomerase, a reverse transcriptase which adds telomeres to 3-prime DNA ends, but telomerase activity declines in oocytes, fixing telomere length earlier during development. Experimentally induced telomere shortening in mice disrupts meiosis, impairs chiasmata formation, halts embryonic cell cycles, and promotes apoptosis in embryos, a phenotype which mimics reproductive senescence in women. Ethical constraints limit study of human embryos to nondestructive assays, such as morphologic evaluation under transmission optics, but cytoplasmic fragmentation is a reliable marker of apoptosis. Study design: Study design consisted of observational study of effect of telomere length in human eggs on cytoplasmic fragmentation, and on other morphologic features of preimplantation embryos. To test the hypothesis that telomere shortening triggers apoptosis in human embryos, we evaluated telomere length as a predictor of cytoplasmic fragmentation in embryos from women undergoing in vitro fertilization. Results: Telomere length negatively predicted fragmentation in day 3 preimplantation embryos, after controlling for patient age and basal follicle stimulating hormone level. Telomere length did not predict other features of preimplantation embryo morphology. Conclusion: The finding that telomere length in human eggs predicts cytoplasmic fragmentation in embryos provides evidence that telomere shortening induces apoptosis in human preimplantation embryos, consistent with a telomere theory of reproductive senescence in women.

Original languageEnglish (US)
Pages (from-to)1256-1261
Number of pages6
JournalAmerican Journal of Obstetrics and Gynecology
Volume192
Issue number4
DOIs
StatePublished - Apr 2005
Externally publishedYes

Fingerprint

Telomere
Fertilization in Vitro
Embryonic Structures
Blastocyst
Telomere Shortening
Apoptosis
Telomerase
Meiosis
Eggs
DNA
Follicle Stimulating Hormone
Germ Cells
Cell Division
Oocytes
Observational Studies
Cell Cycle
Chromosomes
Oxygen
Phenotype

Keywords

  • Aging
  • Aneuploidy
  • Apoptosis
  • Eggs
  • Embryos
  • Meiosis
  • Telomeres

ASJC Scopus subject areas

  • Medicine(all)
  • Obstetrics and Gynecology

Cite this

Telomere length predicts embryo fragmentation after in vitro fertilization in women - Toward a telomere theory of reproductive aging in women. / Keefe, David L.; Franco, Sonia; Liu, Lin; Trimarchi, James; Cao, Benning; Weitzen, Sherry; Agarwal, Shoba; Blasco, Maria A.

In: American Journal of Obstetrics and Gynecology, Vol. 192, No. 4, 04.2005, p. 1256-1261.

Research output: Contribution to journalArticle

Keefe, David L. ; Franco, Sonia ; Liu, Lin ; Trimarchi, James ; Cao, Benning ; Weitzen, Sherry ; Agarwal, Shoba ; Blasco, Maria A. / Telomere length predicts embryo fragmentation after in vitro fertilization in women - Toward a telomere theory of reproductive aging in women. In: American Journal of Obstetrics and Gynecology. 2005 ; Vol. 192, No. 4. pp. 1256-1261.
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