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| Research on the pathogenesis of male infertility obtains new results |
The reporter learned from Huazhong University of Science and Technology that the research group of Professor Yuan Shuiqiao from the Institute of Reproductive Health of the school recently published an online publication on Theranostics (IF=11.
556) entitled "hnRNPU in Sertoli cells cooperates with WT1 and is essential for testicular development by modulating transcriptional factorsSox8/ 9" research paper, this paper first revealed the important role of the RNA-binding protein hnRNPU in Sertoli cells in male infertility, and found that hnRNPU in mammalian Sertoli cells directly regulates important Sertoli cell markers Sox8 and Sox9 The expression of the related target genes to regulate the development of the testis, so as to maintain the seminiferous microenvironment of the testicular seminiferous tubules and the normal development and function of the spermatogenic cells
.
The global number of couples suffering from infertility is as high as 15%, and infertility due to male factors accounts for about 50%
.
Male fertility mainly depends on continuous sperm production.
Sertoli cells can maintain the shape of seminiferous tubules, provide nutrients and physical barrier protection for the germ cells in the seminiferous tubules, and play an indispensable role in the proliferation and migration of germ cells
.
Studies have reported that the lack of certain proteins in Sertoli cells can lead to infertility.
Yuan Shuiqiao’s research group discovered that the RNA-binding protein hnRNPU is expressed in human and mouse Sertoli cells and is highly conserved.
Through Cre/LoxP technology, it was the first to construct a conditional knockout of Hnrnpu gene in testicular Sertoli cells.
Mouse model
.
Phenotypic analysis revealed that male mice lacking hnRNPU in Sertoli cells were completely sterile, their testes were extremely reduced, and they could not produce sperm
At the same time, the research team found that the two transcription factors Sox8/9, which are very important for testicular development, showed a downward-regulation trend in Hnrnpu conditional gene knockout mouse Sertoli cells, and used ChIP-qPCR technology to prove that hnRNPU can directly transcribe with Sox8/9 The combination of the promoter regions of the factors indicates that the hnRNPU protein in Sertoli cells can bind to the promoter region of Sox8/9 and affect their transcriptional activity to regulate important downstream target genes, and ultimately affect the development of the testis
.
The results of this research are expected to further improve the molecular regulation mechanism of male infertility and provide a new theoretical basis for the diagnosis and treatment of non-obstructive azoospermia
The Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology is the first to complete this thesis
.
The 2019 doctoral student Wen Yujiao of the Institute of Reproductive Health and Ma Xixiang, a postdoctoral fellow, are the co-first authors of the paper, and Professor Yuan Shuiqiao is the only independent corresponding author
Related paper information: https://doi.
https://doi.
org/10.
7150/thno.
66819
