Telomere length predicts embryo fragmentation after in vitro fertilization in women—Toward a telomere theory of reproductive aging in women
Received 17 January 2005; received in revised form 19 January 2005; accepted 19 January 2005.
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.
dDepartment of Immunology and Oncology, National Center of Biotechnology, Madrid, Spain
Reprint requests: David Keefe, Dept of Ob/Gyn, Brown University, Woman and Infants Hospital, 101 Dudley St, Providence, RI 02905.
Supported by grants from the Women and Infants Hospital/Brown Faculty Research Fund to D.K., and by the Ministry of Science and Technology (PM97-0133), Spain, and from the European Union (EURATOM/991/0201, FIGH-CT-1999-00002, FIS5-1999-00055) to M.A.B.
Presented at the 23rd Annual Meeting of the American Gynecological and Obstetrical Society, September 9-11, 2004, Bolton Landing, NY.
ABSTRACT