New research suggests that human egg cells may be protected from certain age-driven changes seen throughout other bodies.
The work, published on August 6 in the journal Science Advances, did not explore how its protection works, but highlighted the mitochondria-cell power plants and eggs found in the blood and saliva of adult women. Mitochondria carry their own special DNA, and as the body ages, it mutates. However, there appears to be an exception to this rule within the mitochondria of human egg cells.
Mutations in mitochondrial DNA (mtDNA) are not necessarily harmful, but in some cases they can cause diseases that affect their ability to produce and use energy. These conditions can be life-threatening. There are no approved treatments, and treatments usually focus on relieving symptoms rather than correcting the underlying problem. Thus, it is important to understand whether egg mitochondria pick up more mutations with age, as they can increase the risk of such diseases in children.
You might like it
This can be a factor to consider in family planning. For example, if the risk of disease-causing mitochondrial mutations is very high in older eggs, it could be a discussion for freezing eggs at a younger age, co-author Barbara Arbeithuber, research group leader at the University of Johannes Kepler Lintz in Austria, told Live Science in an email.
Still, it is not the only factor that considers egg quality, as egg cells are known to be reduced in other ways during senescence. And importantly, the new study “is not directly informed of reproductive interventions because it was not the focus of our work,” Arbeithuber said.
“It’s too early to apply these findings to clinical practice,” says Caterina Makova, a study co-author who is a professor of biology in Pennsylvania. “Our results should be replicated in more women and verified in other populations,” Makova told Live Science in an email.
Related: 8-year-olds with rare and fatal illnesses show dramatic improvements in experimental treatment
Eggs were partially “protected” from aging
Studies suggest that at older ages, egg cells pick up new chromosome mutations, and DNA found in the cell nucleus picks up. There is evidence that older oocytes or oocytes cannot repair DNA damage more than younger oocytes. Furthermore, pregnancies occurring at maternal ages over 35 years are associated with a higher rate of chromosomal abnormalities than pregnancies at younger ages. This is due to changes in the egg, and once maturation is reached, it is more likely that there will be an abnormal number of chromosomes.
(In particular, advanced paternal age increases the rate of genetic abnormalities in offspring, so not only eggs but also sperm cells contribute to their mutant burden.)
However, the effect of aging on chromosomal DNA in eggs and sperm has been studied fairly well, but scientists’ understanding of what happens to the mitochondrial DNA in eggs is less clear.
“Previous reports are controversial about human oocytes,” Arbeithuber said. The methods used to analyze DNA in these previous studies were not accurate enough to identify the true rate of mitochondrial mutations. Arbeithuber and her colleagues instead used an approach called the Duplex sequence.
For this study, they recruited 22 women aged 20-42 and had undergone in vitro fertilization (IVF). For each participant, they analyzed blood and saliva samples as well as 1-5 oocytes. In total, they evaluated 80 egg cells in 22 women.
Across all blood, saliva and egg samples, egg mitochondria had 17-24 times fewer mutations than blood and saliva mutations. And its relatively low mutation rate remained stable. The number of mutations seen in the blood increased the most across age groups, followed by saliva, with no statistically significant increase in the number of mutations in the egg.
When the team zoomed in on some mutations that appeared in the eggs, they discovered that it was less likely to affect DNA that was previously linked to the disease than mutations seen in blood and saliva.
“The good news is that unlike what happens in other tissues of the body, such as blood and saliva, human oocytes do not accumulate more mutations as women ages 20-42. “This suggests that the mtDNA in the oocyte is protected from potentially negative effects on aging and cell function,” says Zamberg, who was not involved in the study.
“Overall, this study is relieved for those seeking to conceive a child at a later age, as chromosomal abnormalities increase with mothers’ age, but at least we should not expect a higher level of mutation in their mtDNA,” he said. In particular, he added that the results are confirmed in a large study, as the study included only 22 people.
Next Steps
Before the new study, the same researchers were investigating mitochondrial mutations in mice and monkeys. In mice, an increase in mtDNA mutations was observed with age in both egg cells and other body tissues such as muscles. In monkeys, we found that mutations increased in eggs and other tissues until primates reach about nine years of age. At that point, the rate of mutation in the egg is increasing while other body parts accumulate more and more DNA changes.
“This could be the case for humans too,” suggested Arbeithuber. In other words, eggs accumulate several mitochondrial mutations in their previous lives and may cease at certain points.
Their new study was somewhat limited in that they obtained eggs from people undergoing IVF, so “we were limited by the age of the individuals consulting such clinics,” she added. In the future, it may be interesting to analyze eggs across young ages and generations, from mothers to children, she said.
At this point, researchers don’t know how the mitochondrial DNA in eggs remains preserved over time, but other tissues mutate. “This is an open question,” Arbeithuber said. In their paper, the team proposed that there may be a process that can help eliminate harmful mutations from oocyte DNA, but further research will be needed to confirm this idea.
This article is for informational purposes only and is not intended to provide medical advice.
Source link
