It is known ovarian follicles are the basic unit of the ovary in females and consist of an oocyte, an immature egg, which is surrounded by granulosa cells. Besides being crucial to the development of follicles, studies have shown that granulosa cells possess plasticity that shows stem cell-like properties. Made-to-order oocytes have great potential for preserving fertility and restoring ovarian function, however, it is still unclear whether functional oocytes can be generated from adult female granulosa cells. Now, a study from researchers at the Nankai University introduces a chemical mixture to granulosa cells to induce the production of germline-competent pluripotent stem cells (gPSCs) that were differentiated into functional oocytes in mice. The team states once fertilized, these oocytes were then successfully able to produce healthy offspring, showing no differences from naturally bred mice. The opensource study is published in the journal Cell Reports.
Previous studies show granulosa cells are somatic cells that interact and evolve with oocyte development during maturation of the ovarian follicle in the ovary and exhibit stem-cell-like properties. It is posssible to reprogram granulosa cells to generate iPSCs where they have been successfully used to clone animals. However, this approach uses genetic manipulation, cell transfection, and ectopic expression of transcription factors for iPSCs, as well as embryo destruction for embryonic stem cell derivation. The current study investigates whether granulosa cells can be induced into gPSCs, using a purely chemical approach, to form oocytes that produce fertile mice.
The current study develops a chemical compound containing Rock inhibitor and crotonic acid for the production of gPSCs from granulosa cells. Results show the Rock inhibitor prevents cell death and promotes proliferation, whilst the crotonic acid, in combination with other chemicals, facilitates the induction of granulosa cells into gPSCs that exhibit pluripotency similar to embryonic stem cells. Data findings show when a mixture of Rock inhibitor and vitamin C is introduced to the gPSCs follicular development is improved to induce meiosis, the process of a single cell becoming sex cells, the egg.
The lab states compared with traditional stem cell-inducing methods such as transfection, which reprograms cells by introducing genetic material into somatic cells, chemical treatment provides higher controllability and has a lower risk of genetic instability. They go on to add that gPSCs and oocytes produced from granulosa cells exhibit high genomic stability and successfully produce offspring that show normal fertility.
The team surmises they have successfully reprogrammed granulosa cells to form oocytes using chemical induction, which produced fertile mice. For the future, the researchers state human trials are some time off, with more prospect in preserving fertility and endocrine function, than in treating infertility.
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