A new study on fruit flies has found evidence that oocytes, which develop into eggs, regularly renew the crucial protein connections that hold chromosomes together. This discovery could be a significant advancement in helping women minimize their risk of pregnancy complications as they get older. The research was conducted at Dartmouth College.Risk of pregnancy complications increases as women age, according to a report in the journal Current Biology.
Women are born with the eggs they will have for life, and the connections that hold chromosomes together are formed in those cells before birth. When they reach childbearing age, ovulation causes the egg to divide, creating an egg that can be fertilized. The connections must be in place in the dividing egg to form an egg with the correct number of chromosomes.
As a woman gets older, so do her eggs. The loss of connections as eggs age is oOne factor that increases the likelihood of miscarriages and conditions such as Down syndrome for older women is the maternal age effect. The risk of cell division producing an egg with the wrong number of chromosomes increases significantly after the age of 30.
However, researchers at Dartmouth found that in fruit fly oocytes, new cohesive linkages form on the chromosomes to replace the originals. They observed specific proteins within the cohesin complex, which are responsible for mediating the linkages between chromosomes, and found that this rejuvenation process occurs throughout the development of the fly oocyte.
“We are the first to show that cohesive linkages in oocytes can form after the original linkages are created,” says Sharon Bickel, a professor of biological sciences at Dartmouth and the paper’s corresponding author.
Bickel adds, “It is not known whether organisms other than fruit flies use cohesion rejuvenation in oocytes. However, it is difficult to understand why rejuvenation would be necessary to keep cohesion intact for six days in fruit fly oocytes, but not in human oocytes that undergo decades of aging.”
The researchers suggest in their paper that if human oocytes do have the ability to rejuvenateAs cohesive linkages weaken with age due to oxidative damage, the ability for rejuvenation may decrease, resulting in an overall loss of chromosome linkages, according to Bickel. The Bickel Lab conducts research using fruit flies to study the molecular mechanisms responsible for chromosome cohesion. Their findings indicate that the impact of aging on fruit fly oocytes is comparable to that observed in humans. In 2008, the lab developed a method to artificially age fruit fly oocytes, demonstrating that aging leads to a decrease in cohesive linkages. A paper published in 2016 further revealed that increased oxidative damage contributes to this decline.The aging process in fruit fly oocytes causes a loss of cohesive linkages, according to a study. Another research paper from 2019 found that reducing oxidative damage in aging oocytes can lead to improved cell division outcomes.
According to Bickel, identifying the proteins and mechanisms behind cohesion rejuvenation in this system could help develop therapeutic strategies to enhance rejuvenation in older women’s eggs and slow the loss of cohesion.
Postdoctoral researcher Muhammad Haseeb, the first author of the paper, stated that evidence for turnover in cohesive linkages has been difficult to find in previous research.Researchers have not observed any signs of rejuvenation in experiments conducted in mice so far.
The team at Dartmouth took various approaches to the project, with graduate student Haseeb leading the way. Co-author Katherine Weng, who was a graduate student in Bickel’s lab, generated some of the fly strains the team used.
The researchers were able to manipulate proteins at an earlier stage in oocytes using tools available for fruit fly experiments, while still after the original cohesive linkages had formed. They also used two different methods to monitor a protein.The cohesin complex is present in all types of fruit fly oocytes, according to Haseeb. In contrast, researchers studying mice have been focusing on a single protein that is only found in some cohesin complexes in mouse oocytes, he explains. Haseeb suggests that these differences may explain the findings of the study. The research could potentially lead to further experiments in mouse oocytes, ultimately helping to improve our understanding of this process in humans, he adds. Interestingly, two of the regulatory proteins known to be essential for rejuvenation in fly oocytes are also found on mouse oocyte chromosomes.”After the original cohesive linkages are formed,” Haseeb explains. “This is consistent with them contributing to the rejuvenation process in mammals.”
Bickel and Haseeb have taken the study to the next level in a paper published on June 8 in the journal G3, with co-authors Alana Bernys ’20 and Erin Dikert ’21, who were Dartmouth undergraduate students working on the project. In this paper, the researchers have identified the proteins needed for rejuvenation in order to gain a better understanding of the molecular pathway or pathways.
Another ongoing project in the Bickel Lab involves testing whether nutritional supplements can decrease the risk of chromosome errors in fly oocytes.The article discusses the effects of aging on hats.
