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February 16th, 2007, 13:20 GMT · By Stefan Anitei

Males Are Much Easier to Clone Than Females

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To make a clone, researchers - using a technique called nuclear transfer - take out the nucleus from an unfertilized ovule (oocyte) and replace it with the nucleus from an adult keratinocyte stem cell.

The resulting cells are grown in the laboratory to the blastocyst phase, when the embryo is a small hollow ball of cells. The blastocysts are implanted in a female's uterus, developing into a cloned fetus. "Reprogramming" adult nuclei in this way has very low success rates and normally, in mice for example, only roughly
1-2 % of the blastocysts give birth to clones.

Moreover, cloned animals are often not healthy.

A new research points to the fact that using male cells, scientists could greatly increase their success rates. Male mouse embryos were more than thrice as likely to develop as the female ones, 5.4 % compared to 1.6 %. The team led by Peter Mombaerts and Elaine Fuchs at Rockefeller University in New York, US, employed adult skin stem cells, which are less differentiated and easier to reprogram.

More investigations should be made to see if the sex bias is valid also for other cell types. The oldest of cloned male mice is now nearly two years, which means extremely aged in the mouse world.

Moreover, many of these mice were fertile and healthy. "The difference in cloning rates of male and female stem cells seems likely to involve epigenetics," said Fuchs.

Epigenetic shifts affect a gene's function without impairing its DNA sequence and are reversible.
They can be partially removed from chromosomes during the nuclear transfer process. This epigenetic reprogramming supplants the "memory" of the skin cell's DNA, changing its behavior to an embryonic one.

As one of a female's two X chromosomes is shut down by epigenesis, a female's DNA has to pass through a more complicated epigenetic reprogramming than the male DNA.

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