Asz1 And Mitofusins Play Essential Roles During Spermatogenesis

Gametogenesis is an important biological event during mammalian development. Gametogenesis is specifically referred as spermatogenesis and oogenesis, during which mature sperms and eggs are produced, and eventually go through fertilization to start a new cycle of development.In mammals, spermatogenesis occurs in seminiferous tubules. This process can be divided into four stages including proliferation, growth, maturation and spermiogenesis. In addition, sperms need to further mature and go through capacitation in the epididymis in rodents and human.The spermatogenesis is complicated process which is tightly and precised regulated, thus the investigation of the underlying regulating mechanism for spermatogenesis will contribute to our understanding the origin of life, but also shed light to physiology and pathology human reproduction and diseases.In this study, we found that the germ cell specific protein Aszl was located at mitochondrial outer membrane. We disruptd the mitochondrial localization sequence of Aszl via CRISPR-Cas9 system in mouse. Interestingly, we found Asz1ΔMLS/ΔMLS mice were male infertility with spermatogenesis blocked at meiosis I stage. In addition, we demonstrated that the expression and localizion of Mili/Mvh were altered, and the formation of germ cell RNA biosynthesis granules (known as nuage) was abnormal. Our results therefore revealed mitochondrial localization of Aszl is important to spermatogenesis and nuage formation. We further observed that mitochondrial proteins Mfn1 and Mfn2 interacted with Aszl. Mfn1/2 conditional knock-out mice in germ cells indicated that spermatogenesis was abnormal as well. Specifically, the sperm viability and capacitation were declined, which in turn resulted in male infertility. Taken together, our results suggest that the mitochondrial activity mediated by Aszl and Mfn1/2 were crucial for spermatogenesis.