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Electron micrographs show cells on the surface of the ovary after menopause
.
A series of genetic factors affect the time when the ovaries stop ovulating
A study of more than 200,000 women revealed hundreds of genetic variants related to determining their menopausal age
.
Many of the 290 mutated genes control the body’s response to immature DNA-damaged eggs, highlighting the importance of these processes and suggesting that they can one day be used to extend the life span of humans’ natural reproduction or improve in vitro fertilization technology The success rate
.
The genetic catalog may also help researchers create a diagnostic test that allows women to better predict when they may be menopausal
.
"In an ideal world, we can predict which women have shorter natural childbearing times, so that they can make more informed reproductive choices," said John Perry, a geneticist at the University of Cambridge in the United Kingdom and lead author of the study
Egg inventory
Most people who are designated as women at birth (including cisgender women, transgender men, and some non-intersex and intersex people) have all the cells in their ovaries at birth, and these cells will become their eggs
.
Over time, these cells, called oocytes, will mature into eggs and be released during ovulation
This loss of immature eggs accelerates with age, as the DNA repair mechanism becomes less effective, allowing more damaged DNA to accumulate
.
When menopause comes—usually around the age of 50—the eggs in the ovaries are exhausted
However, the age of menopause varies greatly and is affected by both the environment and genes
.
To understand genetic factors, Perry and his colleagues collected data on 200,000 cisgender women of European descent
The 290 variants found are related to the time of menopause, more than five times the number of genes known to affect reproductive lifespan, and account for about 10% of menopausal age variations
.
Individual variation is related to the advance or delay of menopause, weeks or even years
This gene produces the CHEK2 protein, which can cause cells with damaged DNA to stop dividing, or cause the cells to self-destruct
.
Perry and his colleagues found that the storage time of immature eggs in the ovaries of mice without the CHEK2 gene was longer than in mice with two copies of the CHEK2 gene
In addition, the research team found that mice with an extra copy of the CHEK1 gene had more immature eggs in their ovaries than mice with only two copies of the CHEK1 gene—both at birth and later in life
.
The CHEK1 gene copy is involved in DNA repair
Health effects
The idea of using CHEK protein as a target to delay menopause is not yet ready to be tested on humans, but the results bring hope that treatments that can improve infertility treatment or prolong reproductive life can be developed
.
Even so, researchers still need to be aware that interference with CHEK2 will not lead to the preservation of unhealthy eggs
.
Kutluk Oktay, a fertility expert at Yale University in New Haven, Connecticut, said: "I think there is great hope for strengthening DNA repair in delaying menopause
.
But abolishing checkpoints to remove damaged oocytes may be a risky proposal
.
"
There may also be other health issues: Although postponing menopause is associated with a lower risk of type 2 diabetes and poor bone health, it is also associated with a higher likelihood of hormone-sensitive cancers (such as certain forms of breast cancer)
.
The study's co-author, geneticist Katherine Ruth of the University of Exeter in the United Kingdom, said the research team has not found enough genetic variation to reliably predict whether a particular person will have premature menopause
.
"This is an area that we are confident that we can improve in the future
.
"
One way to improve prediction may be to explain how genetic variation interacts
.
But the time of menopause can also be affected by environmental factors, such as smoking or obesity, which will complicate efforts to use genetics to predict
.
Roberta Venturella, an obstetrician and gynecologist at Catanzaro University in Italy, agrees: "We are talking about a feature involving hundreds (if not thousands) of external factors, such as life>
.
Obviously, we are just at the beginning of a path that will last a long time
.
"
Ruth, KS et al.
Nature https://doi.
org/10.
1038/s41586-021-03779-7 (2021).
