22 September 2021

Ovary in a test tube

Functional follicle grown from stem cells

Maria Tolmacheva, XX2 century

Researchers from Kyushu University managed to recreate the ovarian structures necessary for the formation of mature eggs using mouse stem cells. Moreover, they were able to apply their results to create functional eggs and even grow viable mice.

The work was published in the journal Science (Yoshino et al., Generation of ovarian follicles from mouse pluripotent stem cells). The team hopes that the results obtained will bring us closer to the treatment of female infertility by understanding its underlying causes, and will also serve the cause of the conservation of endangered animal species – through the production of eggs.

In the study of stem cells, it is especially important to understand how one cell, capable of becoming anything, can turn into cells that make up an organ or tissue – this process is called "differentiation". Katsuhiko Hayashi, a professor at the Faculty of Medical Sciences at Kyushu University, is working to uncover the mechanisms underlying the growth and development of the fundamental cell of life – the egg.

An oocyte is an immature stage of an egg. Many important discoveries have been made in understanding the development of oocytes, up to the creation of mouse and human oocytes from the corresponding stem cells and even the breeding of healthy mice. However, one of the main obstacles in this process is the creation of a proper support system that would help turn stem cells into oocytes. In the body, primary oocytes begin to develop during puberty with the support of other cells. The part of the ovary that eventually produces a mature egg is called the follicle.

"Although we were able to artificially create mouse oocytes from stem cells, in order for them to mature, we had to combine them with cells called gonadal somatic cells that were extracted from mice. If we hope to better understand the development of oocytes and apply this technology to endangered animals and even to humans, we should also be able to create a support system from stem cells," explains the first author of the work Takashi Yoshino, Associate Professor of the Faculty of Medical Sciences.

The team's first step was to study mice and identify critical genes that trigger the production of gonadal somatic cells. After identifying these cells, the researchers carefully tested the stem cells of mice under various conditions until they were able to obtain cells with similar characteristics from them.

Scientists have named these cells fetal somatic ovarian cells, or FOSLC. The next step was to combine FOSLCs with primordial germ cells derived from stem cells, the precursors of oocytes, the production of which was worked out during the previous study, and to observe whether they mature into oocytes.

FOSLCs.png

Figure from the press release of Kyushu University Building the ovarian environment from stem cells – VM.

After several days of growth, the cells began to form follicles surrounding the oocytes. After confirming that these cells are in fact fully grown oocytes, the eggs were fertilized and transplanted to a female mouse who played the role of a surrogate mother. As a result, the team of scientists received a brood of healthy mice.

It is expected that the new system will be able to produce a large number of oocytes without the need to take the necessary cells from the host animals.

"This will significantly help improve our understanding of ovarian follicle development and reproductive biology in general. Human use is technically possible, but due to the genetic and epigenetic instability of gametes obtained in vitro, we still have to carefully consider and discuss the ethics and technology of such use. We will continue our work to further clarify both the fundamental and unique mechanisms of reproduction of life," says Hayashi.

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