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Drug protects mice against cancer treatment infertility

11 September 2017
Appeared in BioNews 917

An existing drug has been shown to protect eggs from radiation and chemotherapy damage in mice.

The scientists involved in the study hope this treatment could one day be used to prevent women who undergo cancer treatments from becoming infertile. Currently, egg freezing is their only option.

'That is a serious dilemma and emotional issue,' explained lead researcher Professor John Schimenti of Cornell University, 'when you layer a cancer diagnosis on top of the prospect of having permanent life-altering effects as a result of chemotherapy, and must face the urgent decision of delaying treatment to freeze oocytes at the risk of one's own life.'

Women are born with a lifetime supply of immature eggs but this pool gradually diminishes over time, meaning that older women often have difficulty conceiving. Cancer treatments can also damage oocytes leaving many cancer survivors infertile. Investigation into methods to preserve fertility after chemotherapy is therefore a topic of intense research.

In the study, the scientists treated female mice with a drug that blocks the function of the CHK2 protein. CHK2 normally acts as a quality control checkpoint, and triggers the destruction of any eggs with damaged genetic material. This process prevents harmful mutations from being passed on to offspring.

After being given the CHK2-blocking drug, the mice were treated with radiation, which causes damage to DNA in immature eggs. The researchers found that the oocytes were not destroyed, and when transferred into surrogate mothers could give rise to healthy pups.

Professor John Schimenti noted one major concern: 'Even though these irradiated oocytes led to the birth of healthy mouse pups, it's conceivable that they harbour mutations that will become manifested in a generation or two because we are circumventing an evolutionarily important mechanism of genetic quality control. This needs to be investigated by genome sequencing.'

As blocking the CHK2 quality control mechanism enabled eggs to avoid destruction and to repair damaged DNA over time, this raises the possibility of using a similar method to preserve fertility in humans. 

'While humans and mice have different physiologies, and there is much work to be done to determine safe and effective dosages for people, it is clear that we have the proof of principle for this approach,' said Professor Schimenti.

The study was published in the journal Genetics.

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