By applying a chemical cocktail to granulosa cells, researchers in China induced the cells to transform into functional oocytes in mice. Once fertilized, these oocytes were then successfully able to produce healthy offspring, showing no differences from naturally bred mice. The chemical reprogramming method was published today in Cell Reports.
Granulosa cells tend to undergo cell death and differentiation once removed from the follicles. However when senior author Lin Liu, of the College of Life Sciences at Nankai University, and his team applied a chemical cocktail with Rock inhibitor and crotonic acid they were able to prevent cell death and promote proliferation.
"It's a surprising result," says Liu. "The competency of induced pluripotent germline is usually lower than embryonic stem cells. Germline competency is crucial for germline cells to transfer genetic information to the next generation. With the co-formulation of Rock inhibitor and crotonic acid, it's not only more efficient, but the quality also increased."
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Another cocktail of Rock inhibitor and vitamin C was introduced to the germline-competent pluripotent stem cells to improve the follicle development and induce meiosis.
"We can consistently manipulate the concentration and treatment time of these small chemicals," says Liu. Compared to traditional stem cell-inducing methods such as transfection, which reprograms cells by introducing transcription factors to somatic cells, chemical treatment provides higher controllability. "Transfection method may have a higher risk of genetic instability."
"This is the first time we turned granulosa cells into oocytes, it is a crucial and interesting work in developmental and reproductive biology," he says. "But implementing this research to humans from mice still has a long way to go. I think it has more prospect in preserving fertility and endocrine function, than in treating infertility."
Image: This photo shows a mouse obtained from gPSC4-derived oocytes by IVM and IVF. The mouse is now about one year old. The gPSC4- mice have reproductive ability and produced 13 and 7 pups, respectively, after two matings. Image courtesy of Lin Liu.