Women who are treated for cancer with radiation or chemotherapy may be rendered sterile. Some female breast cancer survivors experience premature ovarian failure, in which they lose normal function of their ovaries.
Women are born with a lifetime reserve of oocytes, or immature eggs, but those oocytes are among the most sensitive cells in the body and may be wiped out by cancer treatments.
Checkpoint protein CHK2 becomes activate when oocytes are damaged by radiation. CHK2 functions in a pathway that eliminates oocytes with DNA damage, a natural function to protect against giving birth to offspring bearing new mutations.
When the researchers irradiated mice lacking the CHK2 gene, the oocytes survived, eventually repaired the DNA damage, and the mice gave birth to healthy pups.
The new study explored whether the checkpoint 2 pathway could be chemically inhibited. There were pre-existing CHK2 inhibitor drugs that were developed, ironically enough, for cancer treatment, but they turned out not to be very useful for treating cancer.
Giving mice the inhibitor drug, a small molecule, it essentially mimicked the knockout of the checkpoint gene.
Inhibiting the checkpoint pathway, the oocytes were not killed by radiation and remained fertile, enabling birth of normal pups.
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