Jumping genes threaten egg cell quality

A woman’s supply of eggs is finite, so it is crucial that the quality of their genetic material is ensured. New work from the Carnegie Institute for Science elucidates a mechanism by which, even before birth, the body tries to eliminate egg cells of the poorest quality. The findings describing this mechanism are published by Nature Communications.

For 50 years, scientists have known that up to 80 percent of a female mammal’s original pool of potential egg cells are eliminated during fetal development through a process called fetal oocyte attrition, or FOA. This phenomenon is conserved in all studied mammals but much about this process remains mysterious.

Previous research indicated that this elimination of potential egg cells during fetal development is related to a transposable element, or “jumping gene,” called LINE-1.

Jumping genes can move around in a cell’s DNA, often breaking genes but sometimes also introducing genetic innovations that improve a species’ survival.

Researchers theorized that purging the cells with the greatest activity by the jumping gene LINE-1 allows for the selective survival of the immature eggs that have the lowest potential of succumbing to jumping genes. The drug AZT, which blocks the multiplication of HIV and LINE-1, temporarily prevented death of immature egg cells. This observation indicated that there was more than one mechanism to detect and eliminate egg cells with excessive LINE-1 activity. The research team used AZT in mice lacking a protein called Chk2, which detects DNA damage and either repairs it or flags the cells where this genetic material is housed for death. When the LINE-1 jumping gene was inhibited by AZT, and the Chk2 protein was rendered ineffective by mutation, the reserve of egg cells increased.

“What’s more, the shutting off the fetal egg cell elimination process in this way did not decrease fertility,” the researchers explained. “This provides further evidence that this is a quality control process undertaken to try to maintain the caliber of the available egg supply.”

More work is needed to determine whether these findings could help combat infertility due to premature ovarian failure by increasing a woman’s total egg supply.

 

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