Mouse oocytes made from stem cells

[Ygggdrasil]

Published today in Nature:

In work that raises the prospect of new infertility treatments and designer babies, researchers have used stem cells to grow fertile mouse egg cells for the first time entirely in a lab dish. The eggs gave rise to pups after being fertilized and implanted into rodent foster mothers. The method—which sometimes produced defective eggs and had a success rate of less than 1%—won’t be producing human egg cells any time soon, but the technique could help researchers identify key genes involved in egg development and maturation.

http://www.sciencemag.org/news/2016/10/mouse-egg-cells-made-entirely-lab-give-rise-healthy-offspring

Citation: Hikabe et al. 2016. Reconstitution in vitro of the entire cycle of the mouse female germ line. Nature. Published online Oct 17 2016. http://dx.doi.org/10.1038/nature20104

Abstract:

The female germ line undergoes a unique sequence of differentiation processes that confers totipotency to the egg. The reconstitution of these events in vitro using pluripotent stem cells is a key achievement in reproductive biology and regenerative medicine. Here we report successful reconstitution in vitro of the entire process of oogenesis from mouse pluripotent stem cells. Fully potent mature oocytes were generated in culture from embryonic stem cells and from induced pluripotent stem cells derived from both embryonic fibroblasts and adult tail tip fibroblasts. Moreover, pluripotent stem cell lines were re-derived from the eggs that were generated in vitro, thereby reconstituting the full female germline cycle in a dish. This culture system will provide a platform for elucidating the molecular mechanisms underlying totipotency and the production of oocytes of other mammalian species in culture.

 

[Greg Bernhardt]

Why such low success rate? What will increase it?

 

[Ygggdrasil]

Why such low success rate? What will increase it?

If I knew the answer to that, I would publish it in Nature :)

It's likely that the researchers don't fully understand all of the factor required for the development and maturation of oocytes. There are likely factors present in the cellular environment that the researchers cannot fully recapitulate in a test tube. These could be growth factors/signaling molecules that are lacking or it could involve mechanical contact with specific types of cells. They are getting close enough that a small fraction can overcome the lack of those factors by chance, but to improve the efficiency would require identifying the missing factors.