Germ cell breakthrough paves way to infertility treatment

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BEIJING - Scientists at Tsinghua University have led the world in inducing in-vitro differentiation of human embryonic stem cells into follicle-like cells. The breakthrough is expected to help the study of premature ovarian failure and improve assisted reproductive technology.

The achievement of the research team led by Professor Kehkooi Kee was published in the latest issue of the academic journal Nature Communications online: http://www.nature.com/articles/ncomms15680

The research showed the differentiation of human embryonic stem cells into follicle-like cells can be achieved under the combined action of two RNA-binding proteins specifically expressed in germ cells, DAZL and BOULE,and growth factors GDF9 and BMP15.

Kee, a Malaysian Chinese scientist, said that unlike somatic cells, germ cells can transmit the genetic chromosomes of the father and mother to the next generation. In the genetic process, germ cells undergo unique meiosis and genetic recombination.

How do the germ cells regulate this process? How do they keep the balance between passing the genes to the next generation and creating a diverse genome? "That is the most interesting question for me in this field of study," said Kee.

However, scientists must overcome difficulties in this field of research. Although they can obtain some human germ cell samples by patient agreement, the sample size is far from enough for molecular experiments and cell experiments.

"We needed to build an in-vitro platform to study the various mechanisms during the process of human germ cell development. So we chose human embryonic stem cells to differentiate into germ cells, including sperms and eggs," said Kee.

In 2009, he and his colleagues used human embryonic stem cells to create human primordial germ cells and sperm-like cells for the first time. They published their research in the academic journal Nature.

Although other scientists have conducted similar experiments, none has made human germ cells differentiate into such a mature state.

After successfully culturing human sperm-like cells in-vitro, Kee's team tried to culture follicle-like cells.

"A follicle is composed of an oocyte and many granulosa cells around it. At first we thought inducing the formation of granulosa cells would be a challenge," Kee said.

But they found growth factors GDF9 and BMP15 could promote the development of follicles.

"We have compared the in-vitro cultured cells with in-vivo cells, and found they have many similar characteristics. But we can only call the in-vitro cells follicle-like, because we can't prove they are exactly the same until we conduct functional experiments," Kee said.

"We hope to improve the efficiency of our experiment, and culture more mature antral follicles to test their function."

Helping the infertile is the aim of the research team.

"Some women cannot have babies because of premature ovarian failure. We might study whether this is caused by gene mutations by conducting in-vitro germ cell experiments, and then develop treatments," said Kee.

The team is also attempting to induce the differentiation of human embryonic stem cells into germ cells on China's first cargo spacecraft, Tianzhou-1 to study the effects of the space environment on human reproduction.