Cell Death Offers Hope For Cancer Treatment
September 23, 2012

Egg Cell Death Proteins Means Hope For Fertility And Cancer Treatment

April Flowers for redOrbit.com — Your Universe Online

Australian scientists from Melbourne have recently found a pair of proteins that cause the death of early egg cells in the ovaries. Blocking these proteins means cells survive the effects of radiotherapy, according to the study in Molecular Cell. The implications of this research could prevent infertility caused by cancer treatments and even stave off menopause.

The team included researchers from the Walter and Eliza Hall Institute, Monash University and Prince Henry's Institute of Medical Research. They looked at egg cells called primordial follicle oocytes. These cells provide each woman's lifetime supply of eggs.

Shortly after birth, a large portion of the egg cells that a female is born with are destroyed. Egg cells continue to die off with age until menopause is complete. Researchers have identified about seven proteins that cause this cell death.

The study found that when the DNA of cells is damaged through chemotherapy or radiotherapy, two of the proteins called Puma and Noxa cause the eggs to die, which causes many female cancer patients to experience infertility problems.

Lowering the number of live egg cells may also cause a woman to go through early menopause.

If the cells were manipulated to not have the Puma protein, they did not die after exposure to radiation therapy.

Professor Jeff Kerr, from Monash University, said, "This might ordinarily be cause for concern because you want damaged egg cells to die so as not to produce abnormal offspring."

"To our great surprise we found that not only did the cells survive being irradiated, they were able to repair the DNA damage they had sustained and could be ovulated and fertilized, producing healthy offspring.

"When the cells were also missing the Noxa protein, there was even better protection against radiation."

The team exposed several types of mice to low doses of radiation; healthy mice, and mice bred to not produce one or both of the proteins. Five days after the irradiation, mice with a full set of proteins had lost all their stored egg cells. Those missing the Puma protein retained 15% of their original store, and mice lacking both Puma and Noxa retained more than half of their egg cells.

In a truly curious twist, when the radiation was pushed up to a level that is half of what it would take to kill the mice, the strain lacking both proteins kept 94% of their egg cell store. The retained eggs appeared healthy as well.

"The really exciting thing is that if you can prevent PUMA and NOXA from killing them, the eggs have a chance to repair their own DNA," says Professor Clare Scott from the Walter and Eliza Hall Institute of Medical Research. "The DNA is remarkably robust."

Scott added, "It means that in the future, medications that block the function of Puma could be used to stop the death of egg cells in patients undergoing chemotherapy or radiotherapy.  Our results suggest that this could maintain the fertility of these patients."

The team claims that the discovery could mean that it is possible to slow the loss of egg cells from the ovaries, delaying early menopause, and perhaps osteoporosis and the heart problems that are associated with it.

Dr. Jane Stewart of the Newcastle Fertility Centre, and a spokeswoman for the British Fertility Society, said, "Potential loss of fertility is an issue which worries many young women undergoing cancer treatment. Whilst it is not always an issue it can be unpredictable and the possibilities for effective fertility preservation in women remain limited."

"Increasing the understanding of the damage done and the potential for directly protecting the ovary and its contained oocytes has to be welcomed and - whilst this work may some way from being translated into clinical practice - it is encouraging as a possible starting point."