男性不育是一个广为关注的全球性问题。遗传是造成男性不育的重要因素之一。在组学大发展的今天，导致男性不育的基因突变被不断鉴定出来。然而，对它们在细胞/亚细胞水平的表型鉴定，以及在分子水平的机制探寻，还大多不尽如人意。申请人以果蝇为模式生物，意外发现果蝇唯一的SNX9家族蛋白SH3PX1功能缺失造成雄性不育，初步结果显示其缺失不影响轴丝的延伸，也不影响个体化复合物的形成，但影响轴丝的形态。值得注意的是，对延伸后的轴丝形态的调控及其在精子发生中的作用还鲜有报道。申请人提出SH3PX1在果蝇精子由圆形精子到成熟精子的过程中发挥重要作用，并拟从细胞/亚细胞水平和分子水平对其具体作用机制进行阐释。本项目的实施将有助于了解SNX9家族蛋白在精子发生中的作用及重要意义，从而加深对精子发生这一基础生物学问题的理解，并为与之相关的男性不育诊断提供理论基础和实践指导。

Male infertility is an attending global challenge. Genetics is one of the major causes for male infertility. In the era of -omics, the list of the genetic mutations that compromise male fertility is ever expanding. However, the phenotypic characterization of the cellular/subcellular changes and the mechanistic interpretation on the molecular level are mostly way from satisfactory. Using Drosophila melanogaster as a model system, we discovered unexpectedly that loss of SH3PX1, the only fruitfly SNX9 family protein, leads to male sterility. Our preliminary results show that loss of SH3PX1 impairs neither the elongation of the axonemes nor the formation of the individualization complexes (ICs). Rather, it undermines the axoneme morphology of the elongated spermatids. Of note, the axoneme’s contribution to spermatogenesis, as long as it has been elongated, seems to follow as a matter of course, and its regulation is also underestimated. We thus propose that SH3PX1 plays essential roles in the spermiogenesis stage of spermatogenesis in Drosophila. We will further elucidate the SH3PX1’s contribution to spermatogenesis not only on the cellular/subcellular level but also on the molecular level. The outcome of this project will uncover the SNX9 proteins’ role and the underlying mechanisms in spermatogenesis, thus improving our understanding of its fundamental biology and providing new insights into the diagnosis of the relevant male infertility.