Thursday, January 31, 2008

Gene Linked to Aging of Ovary in Mice

This incredible image is a human egg with follicle cells, provided by the Science Museum.
The latest issue of Science has this report on the findings of a study that examined the infertility of mice that lacked a particular gene (PTEN). The "News of the Week" piece nicely summarizes the study. Here is a sample:

When a woman is born, her ovaries already contain a full supply of the immature eggs she will need in her reproductive lifetime. Normally, these eggs begin ripening at about age 13 and are gradually released, usually at the rate of one per month, until she is about 50 years old. But in a small minority of women, perhaps 1 in 100, the ovaries stop releasing eggs much earlier in life, thus causing infertility and premature aging. Exactly why that happens isn't understood, but new results may help provide an explanation.

On page 611, a team led by Kui Liu of UmeƄ University in Sweden, reports that a gene called Pten, which is best known as a suppressor of tumor growth, is needed to keep egg development in check. In its absence, the researchers found, the egg-containing follicles of mice were activated rapidly at an early age, thus causing depletion of the animals' eggs much sooner than is normal--a situation similar to that of premature ovarian failure (POF) in humans.

"It is a very nice piece of work that shows the importance of the PTEN pathway" in controlling follicle maturation in mice, says reproductive geneticist Aleksandar Rajkovic of Baylor College of Medicine in Houston, Texas. If PTEN also controls human egg maturation, the finding may aid the design of improved infertility treatments.

Liu and his colleagues came to their conclusion by genetically engineering a mouse strain in which Pten expression was inactivated specifically in the animals' oocytes. The results showed that a functional Pten in oocytes is needed to keep egg follicles from maturing. Without it, Liu says, "all the primordial follicles were activated prematurely."

Once a follicle is activated, there's no going back. Its egg either matures and is released for fertilization or dies. As a result, the animals had one litter but were infertile by about 3 months of age, which is early adulthood for mice. By that same age, their ovaries had lost essentially all their follicles.