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Meiosis continues after puberty, and oocytes develop with granulosa cells during folliculogenesis, giving rise to mature oocytes for reproduction. Embryonic primordial germ cells (PGCs) undergo migration and proliferation, followed by meiosis, which is arrested at diakinesis during prophase I prior to birth. Hence, extensive efforts have been made over the last decades to generate oocytes in vitro, from other source, such as from pluripotent stem cells.Ĭlose interactions between germ cells and somatic cells are essential for ovarian development and function, and can control germ cell proliferation, meiotic entry and arrest as well as formation of the primordial follicle pool. Depletion of oocyte and follicle reserve in vivo makes direct contribution to ovarian aging. In addition, ovarian aging can lead to early menopause and related chronic diseases, such as coronary heart disease, osteoporosis, and endocrine disorders, which seriously affect female reproduction and physical and mental health. Coupled with the influence of diet and environmental factors, the phenomenon of infertility caused by ovarian aging has increased significantly. With the increasing pressure of social competition, many women choose to postpone their childbearing age. ConclusionĮSCs can be induced into embryonic gonadal somatic cell like cells by small molecules. This approach will contribute to the study of germ cell and follicle development and oocyte production and have implications in potentially treating female infertility. After V580 treatment for 6 days and sorted by a surface marker CD63, the cell population yielded a transcriptome profile similar to that of E12.5_GSCs, which promoted meiosis progression and folliculogenesis of primordial germ cells. Through searching for the activators of these pathways, we identified small-molecule compounds Vitamin C (Vc) and AM580 in combination (V580) for inducing differentiation of female embryonic stem cells (ESCs) into E12.5_GSC-like cells (E12.5_GSCLCs).
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Using RNA-sequencing, we identified signaling pathways highly upregulated in E12.5_gonadal somatic cells (E12.5_GSCs). We explored to identify small molecules, which can induce female embryonic stem cells (ESCs) into gonadal somatic cell like cells. It is therefore imperative to achieve an in vitro source of E12.5 gonadal somatic cells. Nevertheless, development of oocytes and follicles from PGCLCs relies on developmentally matched gonadal somatic cells, only available from E12.5 embryos in mice. Excitingly, unlimited oocytes can be generated by differentiation of primordial germ cell like cells (PGCLCs) from pluripotent stem cells. Depletion of oocytes leads to ovarian aging-associated infertility, endocrine disruption and related diseases.