Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China.
Department of Clinical Laboratory, Maternal and Child Health Hospital of Hubei Province, Wuhan, China.
Andrology. 2021 Jan;9(1):368-375. doi: 10.1111/andr.12889. Epub 2020 Sep 9.
Male infertility is a major issue in human reproduction health, yet known genetic factors are only responsible for a small fraction of cases. TSGA10 is a testis-specific protein that is highly conserved among different species. A previous study has reported a homozygous mutation in TSGA10 in a male infertile patient; however, function analysis of Tsga10 genes in knockout mice has not yet been undertaken.
The aim of the present work was to analyse the function of TSGA10 protein in the spermatogenesis of Tsga10 mice.
Tsga10 mice were generated by CRISPR/Cas9 technology, in vitro fertilization (IVF), western blot, co-immunoprecipitation and other methods were used to the function analysis.
Heterozygous Tsga10 male mice created by CRISPR/Cas9 were infertile and presented significantly reduced sperm motility because of disordered mitochondrial sheath formation. Furthermore, TSGA10 can interact with GRP78 and NSUN2, which are associated with peri-implantation lethality and the gonadotropin-releasing hormone (GnRH) network.
We demonstrate that deficiency of Tsga10 gene can lead to male infertility in mice. TSGA10 is involved in the correct arrangement of mitochondrial sheath in spermatozoa. Future studies on TSGA10 include an in-depth exploration of the underlying mechanisms of TSGA10 in spermatogenesis, early embryonic development and GnRH network.
男性不育是人类生殖健康的一个主要问题，然而已知的遗传因素仅能解释一小部分病例。TSGA10 是一种睾丸特异性蛋白，在不同物种中高度保守。先前的研究报道了一名男性不育患者 TSGA10 基因纯合突变；然而，尚未对 Tsga10 基因敲除小鼠进行功能分析。
本研究旨在分析 TSGA10 蛋白在 Tsga10 小鼠精子发生中的功能。
使用 CRISPR/Cas9 技术生成 Tsga10 小鼠，通过体外受精（IVF）、western blot、共免疫沉淀等方法进行功能分析。
CRISPR/Cas9 产生的杂合性 Tsga10 雄性小鼠不育，由于线粒体鞘形成紊乱，精子运动能力显著降低。此外，TSGA10 可与与植入前致死和促性腺激素释放激素（GnRH）网络相关的 GRP78 和 NSUN2 相互作用。
我们证明了 Tsga10 基因的缺失可导致小鼠雄性不育。TSGA10 参与精子中线粒体鞘的正确排列。未来对 TSGA10 的研究包括深入探讨 TSGA10 在精子发生、早期胚胎发育和 GnRH 网络中的潜在机制。
