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Mouse studies suggest fresh approach to fertility preservation

1 October 2012
Appeared in BioNews 675

Two proteins that kick-start the destruction of damaged mouse eggs have been discovered by scientists. The findings may go on to have applications in fertility preservation for female cancer patients who receive aggressive treatment; both radiotherapy and chemotherapy can cause temporary or permanent infertility.

The study, published in the journal Molecular Cell, focused on primordial follicle oocytes - essentially eggs in an immature form which will mature into all the eggs a woman will produce in her lifetime.

When eggs are exposed to radiation or certain chemicals, the resulting damage triggers a process called apoptosis that causes the eggs to self destruct. This is how the body removes potentially dangerous, abnormal cells, but it has unwanted consequences for many women receiving cancer treatment as it can leave them infertile.

The molecular drivers behind oocyte apoptosis are relatively poorly understood, but in their study, Australian researchers discovered two proteins that play a vital role in mice: PUMA and NOXA.

When exposed to radiation, the healthy mice in the study lost all their eggs within 15 days. But when mice that had been genetically engineered not to produce PUMA were exposed to the radiation, 15 percent of their eggs survived. Survival further increased to over 50 percent in mice producing neither PUMA or NOXA.

Dr Clare Scott, at the Walter and Eliza Hall Institute of Medical Research in Victoria, Australia, the lead author of the study, told New Scientist: 'If you can prevent PUMA and NOXA from killing them, the eggs have a chance to repair their own DNA'. The mice in the experiment went on to produce healthy, fertile offspring.

Should PUMA and NOXA be as important in humans, there could be important clinical applications. A drug which blocks the activity of PUMA could potentially be used to prevent fertility loss in female cancer patients.

Another possible use would be to offset the negative effects of early menopause, such as osteoporosis and heart disease, which are currently treated with hormone replacement therapy.

'We know that the timing of menopause is influenced by how many egg cells a female has', said Professor Jock Findlay, head of the Female Reproductive Biology Group at Prince Henry's Institute, in Melbourne, who was also involved in the study. 'Interventions that slow the loss of egg cells from the ovaries could delay premature menopause, prolonging female fertility'.

However, as any drugs that effectively target PUMA or NOXA are yet to be developed such treatments would likely be decades away.

Block egg suicide to guard fertility after cancer therapy
New Scientist |  22 September 2012
DNA Damage-Induced Primordial Follicle Oocyte Apoptosis and Loss of Fertility Require TAp63-Mediated Induction of Puma and Noxa
Molecular Cell |  20 September 2012
Mice experiment may point to new ways to protect female fertility
Reuters |  22 September 2012
New ways to protect female fertility
EurekAlert! (press release) |  21 September 2012
Women undergoing cancer therapy could still have children thanks to protein breakthrough
Mail Online |  24 September 2012
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