Two studies with more than 100,000 women have uncovered a number of genes that help regulate, When a person enters the menopause and thus the duration of their reproductive zest of life 1 , 2 . Some of the genes could also affect the risk of cancer.

The entry age in menopause can vary greatly and is influenced by both environmental and genetic factors. The hope is that these genetic catalogs will help researchers, to develop treatments for infertility and methods for Prediction of the menopause entry age . The studies were on September 11th in Nature 1 and on August 27th in Genetics published .

rare, but effective

These studies are part of a number of current efforts to identify genes that contribute to early menopause. While most of these studies were looking for genetic variants that often occur in the population, the new projects focused on rare DNA sequences, the effect of which is possibly stronger than the frequent sequences.

"You are rare, but typically have a big impact," says Anne Goriiiiel, a geneticist at the University of Oxford, UK, who is not one of the authors of the studies. "New treatments and conceptual progress often come from such rare diseases."

The search for rare genetic variants requires data from a large group of people. In order to receive such data, the geneticist Anna Murray from the University of Exeter Medical School, UK, a co-author of the Nature study, and her colleagues on UK Biobank, an extensive collection of biomedical data , the DNA sequence data and information about the lifestyle and the health of the participants Contains. The researchers focused on protein-encoding DNA and discovered nine genetic variants that are connected to menopause with the entry age. Five of these genes had not previously been associated with the aging process of the ovaries.

women with certain variants of a gene called znf518a , for example, later started menstruation and used to enter into menopause as women who did not have this gene form. The result was a reproductive lifespan, which was shorter for more than six years.

mutations and menopause

A factor that could trigger early menopause is the accumulation of DNA mutations in the ovaries of a person. Such mutations can trigger the repair of the DNA of the eggs or cause the eggs to destroy themselves. The reaction of the eggs to DNA damage is crucial for determining the number of eggs, says Murray. "And the number of egg determines its reproductive lifespan."

mutations can also increase the risk of cancer, and variants in four of the genes that the team discovered were not only associated with early menopause, but also with a higher risk of cancer.

In order to examine the relationship between the accumulation of DNA mutations and ovarian aging, Murray and her colleagues analyzed the genetic sequences of more than 8,000 genetic "tris"-that of a mother, father and child pair.

The team found that women who were associated with frequent DNA variants who were associated with an earlier research with an earlier age of menopause, which were more likely to be made to their offspring.

The results support the idea that DNA damage is related to ovarian aging, says Murray. When the team tried to repeat their experiment with data from another bioank, the results were no longer statistically significant.

Nevertheless, it is important to further research the possible connections between the age to menopause and cancer, says Kári Stefánsson, a geneticist and managing director of the Biopharmafirma Decode Genetics in Reykjavik and Mitartor der Nature -Study. "It draws attention to finding a way to deal with conditions such as early menopause and the influence that it has on biology," he says.

treatment of infertility

In the nature genetics -study, Stefánsson and his colleagues searched for genetic variants associated with early menopause, and focused on variants that only had an influence if they were present in both copies of the DNA of a woman. Your search resulted in a connection between the entry age to the menopause and a gene called ccdc201 , which is known to be only active in immature eggs 2 .

women with certain variants of this gene entered menopause on average nine years earlier. The great effect and specificity of the activity of ccdc201 indicate that this gene is a useful goal to prevent or treat a few cases of Infermentation could prove, says Goriely. Such an intervention would have to be carefully designed to avoid the risk that it will pass eggs damaged to the descendants in the meantime, but in principle eggs already carry significantly fewer mutations than sperm.

"You don't die of infertility, but for many women who suffer from it, it is really a disaster," says Goriiiel. "We should do something for these women."