|Human egg being nourished by a follicle. Image: Wellcome Images|
The thing is that what he'd set out to do is generate new stem cell lines. How he got from one to the other is a serendipitous (and very happy) story.
The work was published September 30 in the Proceedings of the National Academy of Sciences.
Aaron Hsueh had gotten one of our SEED grants and then a Basic Biology grant to to produce mature eggs from ovaries that had been donated by women who had them removed for medical reasons, like cancer. He was trying to develop a source of eggs for somatic cell nuclear transfer (SCNT).
(SCNT is the technique that uses eggs and a cell from an adult to create new stem cell lines that are genetically identical to that adult. It is also used to create cloned animals, like Dolly the sheep. People had been concerned about where the eggs would come from for this technique, and Hsueh thought maybe these donated ovaries might be the answer.)
As part of his CIRM-funded work, Hsueh found some drugs that could help prompt the donated ovaries to produce mature eggs. Here's how we describe the work in our press release:
The recent study also built on what researchers had long-known: that disrupting the ovary could promote follicle growth in some infertile patients. Hsueh worked out the molecular underpinnings of this phenomenon, finding a set of proteins that act as a brake in the ovary to restrain follicle growth. They found that cutting the ovary into smaller pieces could overcome this brake.But here's where the twist comes in. The team realized they could use their technique to generate eggs for SCNT, but it might also stimulate the production of eggs in women with certain forms of infertility.
Hsueh and his colleagues at St. Mariana University School of Medicine in Japan thought that combining the two techniques—breaking up the ovary then activating follicles using the drugs Hsueh had discovered—might be an efficient way of producing eggs. They were right.
Hsueh worked with some colleagues at St. Mariana University School of Medicine in Japan to put that idea to the test. The result: a baby boy. Another women is currently pregnant using the technique.
CIRM President Alan Trounson was a pioneering scientist in the development of in vitro fertilization, which has since produced more than five million children. He commented on Hsueh's work:
“This is an important development for young infertile women who do not ovulate their own eggs and are unable to have children of their own. The fact that this discovery resulted from a CIRM Basic Biology Award shows the value in funding basic science. Removing the inhibition of primary germ cells to grow in the ovary is an important development for reproductive medicine. We never know what important advances will result from scientists probing fundamental aspects of stem cell biology.”As for SCNT, Hsueh says that is no longer a focus of his lab. A team at Oregon Health & Science University succeeded in generating stem cell lines using SCNT last May (we wrote about that here). Hsueh is now hoping to improve his technique to make removing the woman’s ovary unnecessary.