Cell Death Discovery May Help Prevent Infertility, Early Menopause
The discovery of a cell death mechanism may lead to new ways to protect female fertility, bringing hope to women who risk becoming infertile through cancer treatment or early menopause, thanks to a new study from Australia that was published online Thursday in the journal Molecular Cell.
Researchers from the Walter and Eliza Hall Institute, Monash University and Prince Henry's Institute of Medical Research, in Melbourne, were investigating how egg cells die, when they made their discovery.
They found two proteins, PUMA and NOXA, cause egg cells to destroy themselves in the ovaries, and suggest blocking their mechanism could be a target for new treatments that preserve female fertility.
In their paper, they describe how radiation and chemotherapy can damage DNA in cells, causing PUMA and NOXA to trigger cell death.
"PUMA and NOXA can trigger cell death, and have been found to be necessary for the death of many different cell types in response to DNA damage," Associate Professor Clare Scott, from the Walter and Eliza Hall Institute, says in a press statement.
Scott, who is also an oncologist at The Royal Melbourne and Royal Women's Hospitals, explains that triggering cell death is a "natural process" and essential for preserving the health of the body, but obviously for women having cancer treatment who want to have children, it "can be devastating when it leads to infertility".
For the study, Scott and colleagues used mice to study the behavior of primordial follicle oocytes, ovarian cells that are formed in the female fetus, and determine her lifetime's supply of eggs. Low numbers of these oocytes can be a cause of early menopause.
They found that oocytes lacking the PUMA protein did not die after exposure to radiation therapy.
Lead author Jeffrey Kerr, an Associate Professor at Monash University, says while this might be a reason to worry when you want damaged cells to be killed off so as not to produce abnormal offspring, to their great surprise:
"... 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."
And, they also found lack of the NOXA protein protected the cells even more strongly against radiation.
The mice went on to have healthy offspring from the affected cells.
Scott says these results suggest it may be possible to maintain the fertility of patients using techniques based on this discovery:
"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."
The researchers believe the discovery may also help in the prevention of early menopause, since this is governed by how many oocytes a woman is born with.
""Interventions that slow the loss of egg cells from the ovaries could delay premature menopause. As well as prolonging female fertility, such a treatment could have the potential to reduce menopause-associated health conditions, such as osteoporosis and heart disease," says Jock Findlay, Professor and head of the Female Reproductive Biology Group at Prince Henry's Institute.
Funds from the National Health and Medical Research Council, Cancer Council Victoria, the Victorian Cancer Agency, the US Leukemia and Lymphoma Society, the US National Cancer Institute, the American Cancer Society, and the Victorian Government, helped pay for the study.