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


METHODS
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.


CONCLUSIONS
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.
Keefe
David L
DL
Dept of Ob/Gyn, Brown University, Woman and Infants Hospital, 101 Dudley St, Providence, RI 02905, USA. dkeefe@wihri.org
Franco
Sonia
S
Liu
Lin
L
Trimarchi
James
J
Cao
Benning
B
Weitzen
Sherry
S
Agarwal
Shoba
S
Blasco
Maria A
MA
D000328:Adult; D017209:Apoptosis / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics* / Q000502:physiology; D015331:Cohort Studies; D053938:DNA Fragmentation / Q000235:genetics / Q000502:physiology*; D004624:Embryo Transfer; D004628:Embryonic Structures; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D016014:Linear Models; D009865:Oocytes / Q000502:physiology*; D018456:Reproductive Medicine; D012680:Sensitivity and Specificity; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000235:genetics* / Q000502:physiology
D019098:Telomerase