The swapping of sister chromatid tips (green) in a one-celled embryo may lengthen telomeres.


Telomeres go through a growth spurt early in embryonic development, as Lin Liu, David Keefe (University of South Florida, Tampa, FL), and colleagues report. The surge might help restore telomeres whittled down during oocytes' long quiescence.

Size is no issue for sperm, which maintain lengthy telomeres, and researchers assumed that eggs did the same. However, mammalian oocytes stall in meiosis, and for months or years they are besieged by reactive oxygen species that could wear down their telomeres. Supporting that idea, Keefe and coworkers recently reported that human oocytes have short telomeres. The researchers wanted to determine how these structures regrew.

Chromosome caps that were puny in mouse oocytes had stretched dramatically by the two-cell embryo stage, the team found. The stimulus for this growth didn't come from the sperm, because telomeres extended even in oocytes coaxed to develop parthenogenetically.

In stem cells and cancer cells, the enzyme telomerase keeps telomeres luxuriant. However, telomerase contributed little to embryonic elongation, the researchers discovered. Not only was telomerase activity low in oocytes and early embryos, but the chromosome tips grew nearly as long in cells that lack the enzyme as in wild-type cells. “Even with no telomerase activity, we saw lengthening of the telomeres during early development,” says Keefe.

Elongation of the embryo telomeres might instead involve recombination between the tips of sister chromatids. The amount of swapping between telomeres shot up in early embryonic cells. Moreover, two DNA repair proteins—Rad50 and BLM—clustered in the nuclei of early embryos, suggesting that they could be mending telomeres after recombination.

The work indicates that early embryos rapidly extend their shrunken telomeres mainly through recombination. By the blastocyst stage, telomerase kicks in and finishes the job. Embryos might use recombination early on because telomerase can't add large stretches of nucleotides, Keefe says.


Liu, L., et al.
. Nat. Cell Biol. doi:.