Researchers at the University of Montreal Hospital Research Center (CRCHUM) have uncovered a fresh explanation for female infertility linked to aging. Using advanced microscopy, they observed for the first time a specific flaw in the eggs of older mice. This flaw likely exists in the eggs of older women as well. The problem lies in how the cell divides, leading to errors in how chromosomes are distributed.
CRCHUM scientist and University of Montreal professor Greg FitzHarris explained, “The microtubules, which guide chromosome separation during cell division, behave abnormally in older eggs. Instead of forming a balanced spindle, these structures grow in all directions. This disorganized movement seems to cause errors in chromosome sharing, offering a new reason for infertility related to age.
Female mammals, including women, are born with a limited number of eggs. These eggs stay inactive in the ovaries until they are released one by one during menstrual cycles. However, a woman’s fertility starts to drop significantly after the age of 35.
One main cause of infertility in women is the presence of eggs with the wrong number of chromosomes. These are called aneuploid eggs. As women get older, such eggs become more common. This increase explains why older women face greater challenges in becoming pregnant or carrying a pregnancy to term. Additionally, these faulty eggs raise the risk of miscarriage and conditions like Down syndrome in babies.
Previously, scientists believed age-related infertility happened because the “glue” holding chromosomes together weakens with age. This idea is called the “cohesion-loss” hypothesis.
Professor FitzHarris pointed out, “Our research does not contradict that idea, but it reveals another cause: problems with the microtubules. These issues lead to faulty spindles, which then cause errors in how chromosomes are separated.”
Microtubules are tiny tube-like structures that arrange themselves to form a spindle. This spindle gathers chromosomes and divides them evenly during cell division, sending them to opposite sides of the newly forming cells.
In mice, about half of the eggs from older females show spindles with chaotic microtubule behavior, according to FitzHarris.
The team experimented by swapping nuclei between eggs from young mice (6 to 12 weeks old) and older mice (60 weeks old). Shoma Nakagawa, a postdoctoral fellow at CRCHUM and the University of Montreal, explained, “When old eggs had nuclei from young eggs, we still saw problems. This means that the mother’s age affects microtubule alignment independently of the age of the chromosomes.”
FitzHarris’s team also notes that these spindle defects are found in human eggs. The overall cellular machinery in aged eggs does not work as well, but this is not caused by aging chromosomes themselves.
This finding could one day lead to new treatments to help women conceive and sustain pregnancies. FitzHarris said, “We are investigating treatments that might reverse these problems and ‘rejuvenate’ eggs.”
Although more research is needed before such treatments become available, understanding the detailed process of cell division in eggs is an important step. It could help fix errors and ensure the production of healthy eggs ready for fertilization.
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