| Description |
Abnormal gamete (sperm and oocyte) is the main reason for infertility, which is raised by the microenvironment or other inherent reasons. Ovary produces oocytes, the quantity and quality of the oocytes are regulated by the microenvironment. Premature ovarian insufficiency (POI) happened in female under 40 years old, which is often treated by Hormone replacement therapy (HRT), immunotherapy, traditional Chinese medicine therapy and assisted reproduction. However, they could not foundamentally restore the patients fertility. How to restore fertility in the population with low testicular reserve function is another urgent problem to be resolved. Improve the microenvironment of male gamete by using stem leydig cell (SLC), seems to be a new idea for the treatment of sterility. With the development of stem cell technology, the differentiation from pluripotent stem cells into germ cells and even the acquisition of gametes is expected to provide new ideas and methods for infertility. Different from somatic cells, germ cells initially form primordial germ cells (PGCs), with the subsequent differentiation, undergoing transition from mitosis to meiosis of spermatocytes or oocytes, forming haploid germ cells, and eventually sperm or ovum. The successful entry and the completion of meiosis of germ cells are prerequisites for the formation of gametes, but the detailed molecular mechanism remains still unclarified. Here in this project, We produced a stem cell line which could be used for clinical trials, confirmed its safety and validity in mouse POI model, and we also tested its safety in the primary clinical trial; Established primate (monkey) aging animal models and LOH models, the large-scale amplified SLC amplified SLC was transplanted into the testes of aging animals, and its effect on the reconstruction of LC function and the promotion of spermatogenesis was found; Identified that FBXO47, PNLDC1 et. al, are essential for homologous recombination in meiosis, and Cyclin B3 was essential for meiosis I in oocytes, by virtue of the cross-disciplinary research methods, including genetics, biochemistry, cell biology, genomics and proteomics. On the study of primate gametogenesis in vitro, we successfully recapitulated human in vitro spermatogenesis from the male fetal gonad, and differentiated monkey ESC into PGCLC in vitro. All of these reseults lays a foundation for the later research. |
