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Research gives birth to hope for infertility
September 24, 2017, 5:02 pm

Nearly 13 years ago, Professor Jonathan Tilly, a reproductive biologist at Northeastern University in the US, was the first to challenge the long-held scientific belief that humans along with other mammals were born with a set number of eggs and had no ability to create new ones.

Now, Tilly and his colleagues have published a new study which unequivocally shows that stem cells in the ovaries are a critical piece of the mammal fertility puzzle, and may be harnessed to revolutionize fertility treatments and perhaps even delay menopause.

Males from every animal species can produce new sperm at any time. Female flies, fish, and birds can also make new eggs well into their prime. But for decades, the accepted paradigm in reproductive biology was that nature had not granted female mammals the same luxury as their male counterparts.

Professor Tilly first disproved this idea with a study, published in 2004, that found a group of stem cells in mouse ovaries were supporting production of new eggs. His paradigm-shattering discovery was met with debate, disbelief, and disparagement from the scientific community.

Over the years, as research groups all over the world started to confirm and reproduce his results in mice and other mammals, Prof. Tilly sought to show the phenomenon also held true in humans. And in 2012, he did just that by showing that the same group of ovarian stem cells found in mice also existed in reproductive-age women. And he confirmed they served the same function of making new eggs.

In his latest scientific paper published in August of this year, not only reiterated that adult female mice can, and do, create new eggs from stem cells in the ovary, but also quantified the biological importance of these stem cells.

Using a method called suicide gene technology, where researchers can kill and resurrect cells on command, the research team found that mice produce about 60 to 70 new eggs per day. This is a significant number, considering mice only have about 1,000-2,000 eggs in total. And even more importantly, they discovered that as mice age, their bodies slowly turn the transitional stem cells off. The ovarian stem cells are still present in the body, but they stop functioning. As a result, the ovaries stop producing new eggs. Once all the eggs are depleted, the ovaries eventually fail.

"This allowed us to conclude the reason ovaries fail with age isn't because their ability to make new eggs is gone, it's that the house these stem cells live in has fallen into disrepair," the professor said. "So theoretically, to keep ovaries going, you don't want to put more of the stem cells in, you simply want to repair their house."

In his latest study, Prof. Tilly also used a genetic technique called lineage tracing or fate mapping, where instead of removing the stems cells and relying on genetic engineering to mark them, scientists tracked cells in vivo based on their natural self-marking. This allowed the research team to follow the stem cells and confirm they made new eggs and healthy babies under natural conditions. Moreover, they found that those babies went on to have healthy offspring of their own.

“This indicates two important things; first, eggs made during adult life from the ovarian stem cells actively contribute to the pool of eggs that are used under normal conditions to make babies. And secondly, babies made from those newly formed eggs are totally healthy and reproductively fine, and their offspring are totally fine and have no issues," said the professor.

The discovery and understanding of these ovarian stem cells has sweeping implications. One is the possibility of harnessing them to produce an unlimited number of eggs. For women struggling with fertility, this would change everything. Regulating these stem cells may also enable control of the female biological clock. Tilly's lab has achieved this to some degree in mice, successfully halting menopause. Doing so had enormous health benefits on sensory, cognitive, bone, and body mass health in mice. Tilly suspects delaying menopause in women would similarly prevent or delay the multitude of health risks associated with human female aging, although he concedes there is much more work to do before this goal materializes.


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