By Sharon Kirkey. Canadian scientists are working on a way to make older human eggs young again - and maybe even slow menopause - experiments that could make it easier for women in their 40s and perhaps beyond to have babies.
The answer may lie in a single vitamin.
Toronto fertility doctors say their experiments in mice show that co-enzyme Q10 makes older mice produce more and healthier eggs. The doctors are now preparing to test the supplement on women aged 35 and older undergoing fertility treatments.
The work comes as women are pushing back motherhood ever later in life.
Across Canada, pregnancies in women over 35 are increasing, and fertility clinics are seeing more women over 40.
"Our mean age for patients first coming to see us is now 37," said Dr. Robert Casper, medical director of the Toronto Centre for Advanced Reproductive Technology.
Five years ago, it was 33.
Not only do older women find it more difficult to get pregnant, they run an elevated risk of miscarrying or of conceiving embryos with chromosomal abnormalities that cause conditions such as Down syndrome.
A woman is born with all the eggs she will ever have, and by the time she reaches her late 30s, the quality of those eggs begins an irreversible slide. They have less chance of leading to a normal live birth.
Eggs have 46 chromosomes to begin with, but they undergo a change when a woman ovulates. Each egg discards 23 of its own chromosomes and, if it's fertilized, takes in 23 from the sperm cell to replace them. But this takes a lot of energy.
The energy in eggs, and essentially in all human cells, is produced by mitochondria, little power packs inside all our cells. But these weaken with age so that they don't produce as much energy, resulting in a steady decline in tissue and organ function.
"Somebody who is 20 will have eggs with 20-year-old mitochondria in them, and somebody who's 40 will have 40-year-old mitochondria that will produce less energy," said Casper, professor in the division of reproductive sciences at the University of Toronto and a senior scientist at the Samuel Lunenfeld Research Institute at Toronto's Mount Sinai Hospital.
If there isn't enough energy to separate the chromosomes properly, some get left behind.
"They don't get pulled out," Casper explains.
Extra chromosomes can lead to aneuploidy, an abnormal number of chromosomes, the string-like structures that carry our genetic material.
"That's why Down syndrome increases with age - it's all an energy issue," Casper said.
"It's not that there is anything wrong with the eggs, it's just that the batteries have run down."
Casper's team has been studying mitochondria for years, trying to understand whether it's possible to boost energy production in human eggs.
Together with Dr. Andrea Jurisicova, an associate professor in the department of obstetrics and gynecology at the University of Toronto, the researchers originally tried injecting young mitochondria into old mouse eggs, using a preparation made from cordblood stem cells, which are fetal cells, so that the old eggs would have young, healthy mitochondria.
The technique worked - it improved the quality of the eggs and the embryos. The problem was, the embryos had two different mitochondrial DNA - essentially, two different mothers. When Canada's Assisted Human Reproduction Act outlawed mitochondrial gene replacement in 2004, Casper's team abandoned that avenue of research.
Now they're taking a different tack, using co-enzyme Q10.
Mitochondria need co-enzyme Q10 to make energy.
The vitamin is also a powerful anti-oxidant that may prevent mitochondrial DNA damage, Casper said. Co-enzyme Q10's production by the body also decreases as we get older, starting around age 25.
"One of the theories about why we get old and die in the first place is that our cells just run out of energy - the mitochondria stop working properly and there's just not enough energy for cellular function so organs start to fail," Casper said. "A simple explanation could be that there's not enough fuel from the co-Q10 around."
In a pilot study using 52-week-old mice - mid-life for a mouse, and the equivalent of 40 to 50 for a human - Casper's team gave half the group co-enzyme Q10, and the other half a placebo. Next they compared eggs retrieved from both groups of mice with eggs from 10-week-old mice.
"What we found was that just treating the mice with co-Q10 we got more eggs than when we gave them fertility drugs," Casper said. The nuclear spindles that pull the chromosomes apart were more like those in young eggs. The litter size was bigger, and the eggs from the vitamin-treated mice had improved mitochondrial function.
Even more surprising, when the researchers examined the mouse ovaries, there were significantly more egg follicles in the old mice treated with the co-Q10 - suggesting, Casper said, "that we actually were able to delay the onset of the equivalent of menopause in the mice."
The glitch is that the mice were pre-treated for 18 weeks - the equivalent of 10 years or so relative to a human lifespan.
"We might be able to delay menopause, but it might take a decade of pre-treatment," Casper said. The more immediate application might be in improving an older woman's fertility by improving her egg quality. When word got out about his early research on the Internet, women undergoing fertility treatments began taking co-enzyme Q10.
Casper is now trying to recruit women over 35 for a study testing whether taking 600 mg daily of the supplement can lead to a higher number of chromosomally normal eggs.
The rub is that, as soon as the researchers explain the mouse results, none of the women want to be randomized to the placebo group, "especially if they're 40."
The Toronto researchers need 50 women for their study; they're up to 25 so far, after a year-and-a-half of trying.
If the mice experiments hold up in the clinical trials, the implications would be significant, Casper said. "Women could get pregnant easier when they're older."
It also could buoy calls for more single-embryo transfers. For years, fertility clinics have been putting three, four or more embryos back into women over 40 in the hope that at least one would implant and a baby would result.
"If we could improve the percentage of normal eggs, you wouldn't have to put back so many embryos."
The other hope is that, "if we can increase the energy for chromosome separation, then we could eliminate Down syndrome and other chromosomal abnormalities," said Casper.
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