Telomere lengthening early in development.
Stem cells and cancer cells maintain telomere length mostly through telomerase. Telomerase activity is high in male germ line and stem cells, but is low or absent in mature oocytes and cleavage stage embryos, and then high again in blastocysts. How early embryos reset telomere length remains poorly understood. Here, we show that oocytes actually have shorter telomeres than somatic cells, but their telomeres lengthen remarkably during early cleavage development. Moreover, parthenogenetically activated oocytes also lengthen their telomeres, thus the capacity to elongate telomeres must reside within oocytes themselves. Notably, telomeres also elongate in the early cleavage embryos of telomerase-null mice, demonstrating that telomerase is unlikely to be responsible for the abrupt lengthening of telomeres in these cells. Coincident with telomere lengthening, extensive telomere sister-chromatid exchange (T-SCE) and colocalization of the DNA recombination proteins Rad50 and TRF1 were observed in early cleavage embryos. Both T-SCE and DNA recombination proteins decrease in blastocyst stage embryos, whereas telomerase activity increases and telomeres elongate only slowly. We suggest that telomeres lengthen during the early cleavage cycles following fertilization through a recombination-based mechanism, and that from the blastocyst stage onwards, telomerase only maintains the telomere length established by this alternative mechanism.
Liu
Lin
L
Laboratory for Reproductive Medicine, Department of Obstetrics and Gynecology, University of South Florida College of Medicine, Tampa, Florida 33612, USA. liutelom@yahoo.com
Bailey
Susan M
SM
Okuka
Maja
M
Muñoz
Purificación
P
Li
Chao
C
Zhou
Lingjun
L
Wu
Chao
C
Czerwiec
Eva
E
Sandler
Laurel
L
Seyfang
Andreas
A
Blasco
Maria A
MA
Keefe
David L
DL
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D017766:Acid Anhydride Hydrolases; D000818:Animals; D001755:Blastocyst / Q000502:physiology; D004268:DNA-Binding Proteins; D004622:Embryo, Mammalian / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D009865:Oocytes / Q000502:physiology; D010312:Parthenogenesis; D012854:Sister Chromatid Exchange; D019098:Telomerase / Q000502:physiology; D016615:Telomere / Q000502:physiology*; D035321:Telomeric Repeat Binding Protein 1 / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D004268:DNA-Binding Proteins; D035321:Telomeric Repeat Binding Protein 1; D019098:Telomerase; D017766:Acid Anhydride Hydrolases; C495198:Rad50 protein, mouse