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3D printed ovaries produce healthy offspring giving hope to infertile women

Infertile women have been offered new hope after scientists 3D printed ovaries and used them to produce healthy offspring.

In a world’s first, US researchers created an artificial ovary and implanted it into a mouse, which went on to produce eggs, mate successfully, and give birth to healthy pups.

Although the procedure has only been tested on animals so far, the long term aim is to help restore fertility and hormone production in women who have undergone chemotherapy and possibly other infertility issues, such as polycystic ovaries.

Around 24,000 women of child-bearing age are diagnosed with cancer every year in the UK, according to Cancer Research UK.

A scientist holds a bioprosthetic mouse ovary made of gelatin with tweezers - Credit: Northwestern University 
A scientist holds a bioprosthetic mouse ovary made of gelatin with tweezers Credit: Northwestern University

“The real breakthrough here is we’re building a real ovarian prosthesis and the goal of this project is to be able to restore fertility to young cancer patients who have been sterilised by their cancer treatment,” said Dr Teresa Woodruff, a reproductive scientist director of the Women’s Health Research Institute, at Northwestern University, in Illinois.

“Right now, we’re able to do that with young mice and the goal ultimately is to provide this back to patients.

“Using bioengineering to create organ structures that function and restore the health of that tissue for that person, is the holy grail of bioengineering for regenerative medicine. Our hope is that this will be the ovary of the future.”

The prosthetic ovaries were printed using liquid gelatin made from broken-down collagen, a natural material which is found in ligaments, tendons, muscles, bones and skin, researcher reported in the journal Nature Communications.

A mouse that was born from the bioprosthetic ovary lays next to its mother mouse. - Credit: Northwestern University 
A mouse that was born from the bioprosthetic ovary lays next to its mother mouse. Credit: Northwestern University

Dr Alexandra Rutz added: “We have constructed these scaffolds out of gelatin and that is just broken-down collagen, and collagen is what gives us structure in our bones, in our skin”

The ovary walls were engineered to have a lattice-like porous structure, so they could interact with bodily tissues and trigger the production of eggs, while also being strong enough for surgeons to implant.

The sac like structure also allows room for the egg cells to mature and ovulate, as well as blood vessels to form within the implant enabling the hormones to circulate within the bloodstream and trigger lactation after giving birth.

Immature mouse egg after 6 days in bioprosthetic ovary - Credit: Northwestern University 
Immature mouse egg after 6 days in bioprosthetic ovary Credit: Northwestern University

“The purpose of this scaffold is to recapitulate how an ovary would function. We’re thinking big picture, meaning every stage of the girl’s life, so puberty through adulthood to a natural menopause,”  said Dr Monica Laronda, co-lead author of this research.

“What happens with some of our cancer patients is that their ovaries don’t function at a high enough level and they need to use hormone replacement therapies in order to trigger puberty.

“Our technician removed the ovary of the mouse, replaced it with out scaffold, stitched it all back up and we mated some of those animals and we were able to get live birth.”

A microscopic image of an immature mouse egg, surrounded by supportive cells and housed in a scaffold with multiple layers of gelatin.   - Credit: Northwestern University 
A microscopic image of an immature mouse egg, surrounded by supportive cells and housed in a scaffold with multiple layers of gelatin. Credit: Northwestern University

The team is now working on enlarging the scaffold so that it could be in tested on larger animals, and eventually humans.

Many cancer treatments can impact fertility because women are born with all their eggs and are unable to produce more if they are damaged. In some cases chemotherapy can trigger sterility and early menopause.

Women can choose to have embryos, eggs or ovarian tissue frozen before treatment but that can be difficult with certain types of cancer, such as ovarian or breast cancer. It can also take weeks to stimulate the ovaries and college the eggs, and specialists often want women to start treatment immediately.  

Martin Ledwick, Cancer Research UK’s head cancer information nurse, said: “Fertility preservation is an important issue for many patients whose treatment is likely to leave them infertile. 

"It’s good to see research into new ways that might maintain fertility. But so far this work has only been done in mice so it’s not yet clear whether it might be useful for people in the future.”

However a recent study by Edinburgh University found that in one case, a drug combination used for Hodgkin’s Lymphoma known as ABVD actually triggered the development of new eggs.

The male mouse that was created from the original bioprosthetic ovary transplant was able to mate with a non-green mother, and father a litter of mixed (green and not-green) pups. - Credit: Northwestern University 
The male mouse that was created from the original bioprosthetic ovary transplant was able to mate with a non-green mother, and father a litter of mixed (green and not-green) pups. Credit: Northwestern University

The researchers proved it is possible to reverse the clock and coax the ovaries back into a pre-pubescent state where they begin to produce new eggs.

The discovery came after scientists noticed that women who had undergone chemotherapy had up to 10 times the number of eggs as healthy women.

The researchers speculated that the shock of chemotherapy may trigger stem cells in the ovaries into producing new follicles, the hollow hair-like structures which each produce a single egg.

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