Mouse studies suggest fresh approach to fertility preservation

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.