Lab-made eggs may provide new hope for infertile women
Advances in stem cell research are ongoing in many areas. On October 4, Japanese researchers reported that they had produced viable mouse eggs from stem cells in a laboratory dish, which were fertilized and developed into healthy newborn mice. They published their findings in the journal Science.
Lead author Katsuhiko Hayashi noted that making mouse eggs was more difficult because, unlike sperm, ova are large and fragile and they mature only after a long, complex process. It will be even more difficult to repeat in humans. However, if it can be accomplished, it could potentially revolutionize reproductive medicine by enabling both infertile men and women to conceive their own genetic offspring. The stem cells used to produce both the sperm and ova were embryonic stem (ES) cells and induced pluripotent stem (iPS) cells. The former are taken from embryos and the latter are adult tissue cells that are reprogrammed to perform like stem cells. In theory, both can produce all of the body's cell types; however, most researchers have been unable to turn them into germ cells, precursors of sperm and eggs.
Past efforts did grow sperm and eggs; however, did not develop into healthy and long-lived mice. In the present study, the researchers created new mouse eggs in the lab, and then used them to create healthy and long-lived offspring. The results were achieved using both types of stem cells, the embryonic and the reprogrammed; thus, validating the technique in a mouse model. The researchers first determined which proteins naturally turn primordial cells (a stage between stem cells and specialized cells) into either ova or sperm. Then they add the same proteins to stem cells in a laboratory dish and see if it yields the same result.
The investigators began by adding proteins, known as growth factors, to stem cells obtained from a female mouse. Because the proteins control cell growth and differentiation, the stem cells became epiblast-like cells, which are a certain type of cell in the early embryo of a mammal. When other proteins were added, the epiblast-like cells became primordial germ cells. Primordial germ cells are not of a particular sex; however, they can become eggs or sperm depending on which somatic cells surround them. Somatic cells are non-germ cells that evolve into forming bodily structures such as blood, bone, and the organs.
The scientists obtained a fetal mouse ovary and removed its germ cells; however, they left the somatic cells in place. The previously-developed primordial germ cells were cultured with the somatic cells, and the mix was transplanted into an adult female mouse. Four weeks later, scientists removed the transplanted cells and isolated the immature eggs that had developed; the cells were then matured in a laboratory dish where they matured. The eggs were placed in a test tube and fertilized with mouse sperm. The resulting embryos were transferred to female mice, some of which yielded healthy and fertile mice pups. The researcher noted that the fertilization rates using lab-made eggs roughly matched the rate using natural mouse eggs. However, the final outcome of the experiment was less efficient. In a control group, where natural mouse eggs were used, approximately 13% of transferred embryos led to healthy, fertile pups. By comparison, the percentage was 3.9% for lab-made eggs created from embryonic stem cells, and 1.8% for lab-made eggs created via reprogramming.
The researchers note that the production of human ova and sperm from stem cells would raise major ethical questions. Theoretically, it would allow a man or woman of any age, or even someone who is dead but whose tissues are preserved, to become a parent. There is no guarantee the technique would work on human cells. For example, the growth-factor proteins that function in mice are different than the ones needed for human cells. Despite the foregoing, the experiments by the Japanese researchers are likely to offer useful insights into how a primordial cell gets converted into a specialized egg or sperm, a process that is currently poorly understood.