One out of every ten women in the United States between the ages of 15 and 44 faces reproductive challenges, according to the Centers for Disease Control and Prevention [1]. These challenges have a number of causes, including ovulation disorders and blockage of fallopian tubes. Although in vitro fertilization might be a treatment option for these women, the procedure is invasive because eggs need to be surgically removed from the ovary. Moreover, if a woman is incapable of producing healthy eggs, then it is currently impossible for her to have genetically-related children [2].

In the future, women suffering from infertility might be able to have genetically-related babies by donating a small piece of their skin to be developed into an egg. Scientists are now able to take skin cells from mice, reprogram them into stem cells, and generate eggs from these stem cells. What’s more, these eggs can be fertilized to generate viable, normal, and fully fertile offspring! This scientific breakthrough came from the laboratory of Dr. Mitinori Saitou at Kyoto University, and was reported in the journal Science in early October 2012 [3].

The science behind the breakthrough

Stem cells are pluripotent, which means they have the potential to develop into any kind of cell that we have in our bodies. By exposing stem cells to different chemical and genetic signals, scientists have successfully coaxed them to become different body cells, including nerve cells, liver cells, and heart cells. However, Saitou’s study was the first time that fertile eggs had been produced from stem cells. (Last year, their group also made functional sperm from stem cells. See reference [4] if you are interested in learning more about that!)  Saitou’s group successfully turned two different types of stem cells into eggs: embryonic stem cells, which can be isolated from early embryos, and induced pluripotent stem cells (iPSCs), which can be generated from skin cells, blood cells and some other cell types by the introduction of embryonic genes in a process called genetic reprogramming [5].

There are a lot of steps involved in generating eggs from skin cells (see figure).  First, researchers reprogrammed the skin cells to become iPSCs by introducing embryonic genes as mentioned above. Next, they induced the iPSCs to become germ cells (reproductive cells that can develop into eggs or sperm) by exposing them to specific chemical signals. They then mixed the induced germ cells with somatic cells (non-germ cells) from a mouse ovary, so that the germ cells would be exposed to signals that are normally provided by other cells in the ovary. These reconstituted ovaries were transplanted into another mouse, under the membrane that houses the ovary. After about a month, the scientists isolated eggs from the reconstituted ovaries and allowed them to further mature in a culture dish. Finally, the mature eggs underwent in vitro fertilization and the embryos were transferred into the uteri of surrogate mother mice. The mice born from these surrogates were not only viable, but also grew normally into fertile adults capable of producing their own offspring [3][6][7].

From mice to humans

The publication of this research has stimulated a lot of interest, both in the scientific community and among the general public. It serves as a proof of principle that stem cells can develop into fully functional egg cells, and furthermore that iPSCs, or non-embryonic stem cells, have this ability. Because mice and humans are biologically similar, it might be possible for this approach to be translated to human cells. If this treatment becomes available for people, it will allow infertile women and women who have passed their reproductive age to have genetically-related babies.

Despite these promising findings, there are many technical and ethical concerns to address before this method can be applied to humans. For example, scientists must find a way to develop germ cells into mature eggs outside of the body, as ovary transplantation is both technically challenging and invasive. Furthermore, testing whether the eggs are functional may be difficult, as researchers cannot simply fertilize the eggs and see if they turn into healthy babies. Functional testing could be done in the context of fertility treatment, but these eggs would not be suitable for use in fertility treatment until scientists are confident that they have a good chance of leading to healthy pregnancies and healthy babies [7]. Regulations will also be necessary to ensure that this technology does not pass into the wrong hands. As Ronald Green, a bioethicist at Dartmouth University said, “Any skin cell that you can find on the edge of a coffee cup theoretically could be induced back to being an egg, and a baby could be produced. When you think about the commercial possibilities of people selling to infertile people babies produced from George Clooney or Jennifer Aniston, or whatever, you have to worry about it” [8].

Given that this technology may help the 6.7 million women in the US facing reproductive challenges, not to mention women in the rest of the world, translating it into a human therapy is a worthwhile goal. However, it will be important to move carefully and make sure the technical and ethical issues are thoroughly addressed.  Even though this technology may not be applied in humans for many years, the ability to use stem cells to produce both sperm and egg cells that can go on to produce viable, fertile offspring is a fundamentally huge scientific breakthrough!

Kevin Chau is a graduate student in the Biological and Biomedical Sciences Program at Harvard University.

References

[1] The Centers for Disease Control and Prevention <http://www.cdc.gov/nchs/fastats/fertile.htm>

[2] American Pregnancy Association <http://www.americanpregnancy.org/main/statistics.html>

[3] Hayashi, et. al. (2012) Offspring from Oocytes Derived from in Vitro Primordial Germ Cell–Like Cells in Mice. Science. <http://www.sciencemag.org/content/early/2012/10/03/science.1226889>

[4] “Scientists Restore Fertility in Mice Using Lab-Generated Sperm” by Meredith Melnick, TIME <http://healthland.time.com/2011/08/05/scientists-restore-fertility-in-mice-using-lab-generated-sperm/#ixzz296anAAsP>

[5] National Institutes of Health – Stem cell Information <http://stemcells.nih.gov/info/basics/basics2.asp>

[6] “Baby Mice Born from Eggs Made from Stem Cells” by Katherine Harmon, Scientific American <http://blogs.scientificamerican.com/observations/2012/10/04/baby-mice-born-from-eggs-made-from-stem-cells/>

[7] “From Stem Cells to Eggs (And Beyond)” Ira Flatow’s interview with Dr. Sean Morrison, National Public Radio <http://www.npr.org/2012/10/05/162372205/from-stem-cells-to-eggs-and-beyond>

[8] “Scientists create fertile eggs from mouse stem cells” by Rob Stein, National Public Radio <http://www.npr.org/blogs/health/2012/10/04/162263750/scientists-create-fertile-eggs-from-mouse-stem-cells>