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Gene defect 'causes early menopause'

Catherine McDiarmid-Watt | Friday, February 23, 2007 | 0 comments

Scientists have discovered a genetic fault which could cause women to go through an early menopause.

They say the discovery of the fault, which influences what happens within the ovary, could one day lead to the development of a contraceptive which could also delay the menopause.

Tests in mice showed that those animals engineered not to have a particular gene went through an early menopause, also known as premature ovarian failure.

Most women go through the menopause at around the age of 50. If a woman experiences the menopause before the age of 40, it is said to be premature.

US researchers say their tests on mice could help understanding of the condition, which affects around one in 1,000 women in their 30s.


The research concentrated on one of a family of genes responsible for "switching" the actions of other genes on or off.

These "forkhead" genes are thought to control processes involved in ageing, cancer and diabetes.

The scientists focussed on a gene called FOXO3a.

They created mice which lacked both copies of the gene.

As the females aged, they produced smaller litters.

By the time they were 15 weeks old - equivalent to early adulthood in a woman - they were sterile.

It was found that the follicles within the mice's ovaries that contain eggs had been activated earlier and much more widely than in the females with the FOXO3a genes.
When a follicle is activated, it moves from the "resting pool" - a female's entire repository of eggs - to the "growing pool" and begins the maturation which is necessary before the egg can be released in ovulation.

But if a follicle is activated too early, it and the egg within it dies.

The researchers say that this means the mouse uses up her lifetime supply of eggs much more quickly than she should do - and the same could apply to women who go through a premature menopause.

They suggest that if the FOXO3a gene is not working as it should, follicle activation is not regulated properly.

The researchers said more research is now needed to see if the same results are seen in women.

But they predicted it may one day be possible to develop a contraceptive that would delay follicular activation, keeping follicles in the resting pool until a woman wants to become fertile.

Existing oral contraceptives stop the release of egg, but do not slow the rate of activation.


Dr Diego Castrillon, of the Brigham and Women's Hospital in Boston, who led the research, said:
"Our findings raise the possibility that increased activation of eggs over a woman's lifespan could result in premature ovarian failure and early menopause."
Dr Ronald DePinho of the Dana-Furber Cancer Institute, who had been looking at forkhead genes role in cancers, also worked on the study.

He said: "This provides a molecular foothold into a process that we knew little about - that is, the mechanism that constrains or triggers the activation and maturation of the egg."

Professor William Ledger, a consultant in obstetrics and gynaecology at the University of Sheffield, told BBC News Online: "There is a list of candidate genes that may be involved in the regulation of ovarian function.

He said it was not yet possible to design drugs that could over-ride the genetic fault.

But he added:
"It could be possible to look at women from families with a history of early menopause, and there are a lot of them, and see if they are carriers of the gene.

"If they are, women could be advised to have their families early."

The research is published in the journal Science.


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About Catherine: I am mom to three grown sons, two grandchildren and two rescue dogs. After years of raising my boys as a single mom, I remarried a wonderful man who had never had a child of his own. Unexpectedly, I found myself pregnant at 49!
Sadly we lost that precious baby at 8 weeks, and decided to try again. Five more losses, turned down for donor egg, foster care and adoption due to my age and losses - we have accepted that there will be no more babies in our house.

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