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They decipher the genetic map that opens the door to predict menopause

A scientist in a laboratory, in a file image. (Photo: Nicola Tree via .)

Women are born with all the eggs they will have throughout their lives and these are progressively lost with age. Now, a scientific team of more than 180 institutions has identified 290 genetic variants that influence menopause and the reproductive life of women. This also opens the door to better predict which women could reach menopause earlier.

This genetic map –56 of these variants had already been identified previously– has been published in the journal Nature and substantially delves into the knowledge about the reproductive process, according to those responsible.

The scientific team, which also successfully manipulated key genes associated with these variants in mice, thus increasing their reproductive life, is co-led by researchers from the British universities of Exeter and Cambridge, the University of Copenhagen and the Spanish Autonomous University of Barcelona ( UAB).

The study may serve as the basis for future research on new therapeutic approaches for infertility treatments and disease prevention, the journal summarizes.

Reproductive aging

Despite the fact that life expectancy has increased dramatically in the last 150 years, the age at which most women go through menopause has remained more or less constant, on average around 50 years. from the UAB and Exeter.

Women are born with all the eggs they will have throughout their lives and these are progressively lost with age, which is known as reproductive aging. Thus, menopause occurs once most of these eggs have disappeared, despite the fact that natural fertility decreases substantially earlier.

Although this knowledge is also essential for healthy aging – the onset of menopause could increase the risk of bone disease or type 2 diabetes – reproductive aging has been difficult to study and the details about the underlying biology are still quite a lot. limited.

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Different genetic bases of more than half a million women

To advance in this field, the scientists analyzed data, from different genetic bases, of more than half a million women in whom menopause occurred between the ages of 40 and 60: most were of European descent, but also included nearly 80,000 of East Asian descent, with similar results.

The examination of some 13.1 million genetic variants identified 290 linked to ovarian aging, of which many are related to DNA repair processes. “We have seen that the main mechanism to which these variants are associated is related to DNA repair”, points out the Spanish Ignasi Roig, one of the authors of the work and head of the team at the UAB Institute of Biotechnology and Biomedicine.

And it is that the mechanisms that control the quality of DNA and regulate how it is repaired when there is damage are very important for maintaining the number of eggs and the ovarian foundation, adds Roig. Also, remember that menopause is associated with a decrease in the number of eggs, so the longer these remain in the ovaries, the later the cessation of menstruation will come.

Two genes: CHEK1 and CHEK2

Specifically, the scientists looked at two genes that regulate a wide variety of DNA repair processes – CHEK1 and CHEK2 – and found, in experiments in mice, that both when CHEK2 is removed to stop working and when CHEK1 is overexpressed to increase its activity the duration of the reproductive life increases by 25% (among others, the eggs take longer to be depleted).

But the reproductive physiology of this animal differs from that of women in several ways, including that they do not have menopause. For Roig, this fact does not distort the conclusions of the study because, although they do not undergo menopause, they do have an aging process of ovarian function very similar to that of women.

In addition, the team examined the onset of menopause in women who do not naturally have the active CHEK2 gene and found that they reach it about 3.5 years later than those with a normally active gene. On the other hand, they found that the mutation in the Brca1 gene leads to early menopause (2.63 years).

In this regard, Katherine Ruth, from the University of Exeter, says: “We hope that our work will help provide new possibilities to help women plan for the future.”

The researchers also evaluated the health impact of a previous or later menopause. They found that an early menopause increases the risk of type 2 diabetes and is linked to poorer bone health and an increased risk of fractures, but decreases the risk of some types of cancer, such as ovarian and breast cancer.

“This research is incredibly exciting,” emphasizes John Perry, from the University of Cambridge, who concludes: although there is still a long way to go, “we now know more about the mechanisms that regulate reproductive aging in women”, It will help to avoid some health problems.

The next step, according to Roig, is to study in animals how to lengthen the egg reserve using drugs.

This article originally appeared on The HuffPost and has been updated.

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