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Studies in mice reveal a genetic link to early menopause

4 February 2008
Appeared in BioNews 443

An international team of scientists has discovered a genetic defect in mice that may be linked to premature menopause. The study, published in Science, found that a gene called PTEN (phosphatase and tensin homolog protein) controls the life cycle of eggs in the ovaries, and that mice lacking PTEN have a shorter reproductive life. The findings have wide-reaching implications for the treatment of infertility and IVF.

All women are born with a finite number of eggs - generally between 300 000 and 400 000 - in their ovaries. Each egg exists in a premature state in an individual tiny sac called a primordial follicle. After a woman has reached puberty, around a dozen of her eggs are activated each month and begin to mature. Of these, one will reach full maturity and will be released into her fallopian tube. The remaining activated eggs undergo an automatic programme of destruction, and the following month the process begins afresh with a new set of immature eggs. After all of a woman's eggs are used up in this way, she will undergo the menopause. The age of onset of the menopause is therefore determined by the number of eggs a woman is born with, and the rate at which these eggs are depleted during her monthly cycles.

The researchers, led by Professor Kui Lui of Umea University in Sweden, found that mice lacking the PTEN gene became infertile in the equivalent of early adulthood in humans. All their eggs became activated early, using up their entire reserve of immature eggs within their first few monthly reproductive cycles. Professor Ilpo Huhtaniemi of Imperial College London helped to oversee the study. He described PTEN as 'a kind of brake' that prevents the eggs from ripening prematurely and exhausting the supply. He told the Daily Telegraph newspaper: 'we have one good candidate to explain why some women develop premature menopause' and that they plan to investigate this further in humans.

If a similar genetic mechanism is found to control ovulation in humans, then it is hoped that developing a drug that mimics the effects of PTEN will provide a new means of preventing or treating early menopause. Furthermore, PTEN may also prove to be a helping hand in IVF, providing a new way to ripen eggs in the laboratory. Professor Liu explained: 'previously, it was not possible to use the sleeping primordial follicles for IVF, as they are not able to grow up in a culture dish...[Now it is possible] to trigger the growth of primordial follicles by using synthetic PTEN inhibitors'. He concluded: 'this will mean that a much richer resource of follicles can be used for IVF'. This would be of great benefit to infertile women and women hoping to freeze embryos prior to starting chemotherapy or radiotherapy for cancer.

Oocyte-Specific Deletion of Pten Causes Premature Activation of the Primordial Follicle Pool
Science |  1 February 2008
Scientists discover enzyme that controls ovulation
The Daily Telegraph |  31 January 2008
Study Spots Gene That Plays Role in Infertility
US News |  31 January 2008
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