Research on Fruit Flies May Help Elderly Women’s Eggs

Sharon Bickel and Muhammad Haseeb

The work was directed by Professor of Biological Sciences Sharon Bickel and first author Muhammad Haseeb, Guarini ’24. (Photo courtesy of Bickel Lab.)

The first proof in any organism that oocytes, or the cells that develop into eggs, periodically renew the vital protein bonds that hold chromosomes together comes from a Dartmouth study carried out on fruit flies. The researchers describe their findings in the journal Current Biology, suggesting that they represent a potentially significant step in assisting women in lowering their risk of pregnancy difficulties as they get older.

The cohesive links that connect chromosomes are formed in those cells during pregnancy, and women are born with the oocytes they will have for the rest of their lives. When they are ready to have children, ovulation causes the oocyte to split, creating an egg that a sperm can fertilize. In order for the dividing oocyte to produce an egg with the appropriate number of chromosomes, cohesive connections must exist.

A woman’s oocytes age with her. The maternal age effect, which raises older women’s risk of miscarriages and having infants born with abnormalities like Down syndrome, is attributed in part to the loss of coherent connections as oocytes age.

Beyond the age of thirty, there is a large increase in the likelihood that cell division may result in an egg with an incorrect number of chromosomes.

However, the Dartmouth scientists found that fresh cohesive connections replace the old ones on the chromosomes in fruit fly eggs. They observed certain proteins in the cohesin complex, which is a collection of proteins that mediates chromosomal connections, and discovered that this process of rejuvenation continues during the fly oocyte’s development.

“We are the first in the field to show that cohesive linkages can form in oocytes after the original linkages are generated,” says Dartmouth biological sciences professor and paper’s corresponding author Sharon Bickel.

It is unknown, according to Bickel, if creatures other than fruit flies make use of cohesion renewal in oocytes. “However, it is difficult to comprehend why rejuvenation would be required in fruit fly oocytes to maintain cohesiveness for six days, but not in human oocytes that experience decades of aging.”

In their study, the researchers hypothesize that oxidative damage brought on by aging may lead this process to become less effective, even if human oocytes are capable of rejuvenating cohesive connections. According to Bickel, a reduction in rejuvenation may result in a general loss of chromosomal connections.

The Bickel Lab investigates the molecular processes underpinning chromosomal cohesion using fruit flies as a model organism. Researchers have discovered that fruit fly oocytes age similarly to human beings. The researchers revealed a technique for “aging” fruit fly eggs in 2008, which showed that aging results in a loss of coherent connections.

A lab article from 2019 revealed that reducing oxidative damage in aged oocytes enhances cell division outcomes, whereas a 2016 paper shown that increasing oxidative damage in fruit fly oocytes also resulted in the loss of cohesive connections.

The first author of the work, Muhammad Haseeb, Guarini ’24, a postdoctoral researcher in Bickel’s group, notes that researchers have not been able to find any indication of turnover in cohesive links. Thus far, research conducted on mice has not revealed any indications of regeneration.

According to Haseeb, who started the experiment as a graduate student in the Molecular and Cellular Biology program, the Dartmouth researchers used a variety of strategies. Co-author Katherine Weng, Guarini ’14, created a few of the fly strains that the team used during her time as a graduate student in Bickel’s lab.

With fruit fly trials, the technologies available to the researchers allowed them to modify proteins in oocytes at an earlier stage, but after the formation of the original cohesive connections. Additionally, according to Haseeb, they employed two distinct techniques to keep an eye on a protein present in every variation of the cohesin complex discovered in fruit fly oocytes. According to him, a subgroup of cohesin complexes in mouse oocytes included a particular protein that attracted the attention of researchers studying mice.

According to Haseeb, “it’s possible that one or both of these differences account for our findings.” According to him, the publication could make it easier to do more research using mouse oocytes, which might pave the way for a better knowledge of this process in humans.

Haseeb notes that it’s interesting to note that two regulatory proteins that are known to be necessary for rejuvenation in fly oocytes are also present on the chromosomes of mouse oocytes—after the initial cohesive links are created. “That is consistent with their involvement in mammal rejuvenation.”

In a study co-authored by undergraduate students Erin Dikert ’21 and Alana Bernys ’20, published June 8 in the journal G3, Bickel and Haseeb expand on the research. In order to get a better understanding of the molecular route or processes, the researchers identified proteins necessary for rejuvenation in this study.

Testing whether dietary supplements might lower the likelihood of chromosomal mistakes in aged fly oocytes is another current topic in the Bickel Lab.