The Function And Mechanism Of Mitofusion During Spermatogenesis In Mice

Mitofusin-1 and 2(MFN1 and MFN2)are highly conserved transmembrane GTPases which play critical roles in mitochondrial fusion in mammals.Recent data have demonstrated that MFNs are involved in the regulation of several crucial biological processes beyond mitofusion,including mitochondrial metabolism,cellular signaling cascade,apoptosis,and proliferation.In male reproduction system,there are three phases in spermatogenesis,including spermatogoniogenesis,meiosis of spermatocytes,and spermiogenesis.The number,size shape,and distribution of mitochondria undergo dramatic changes throughout these processes.To determine the role of MFNs in mammalian germ cell development,we derived mice carrying conditional knockout of MFN1 or MFN2.Here,we showed that germ cell-specific MFN1-or MFN2-knockout mice were male infertile and displayed obvious defects in size and weight of testes from two weeks mice.Furthermore,the development of germ cells were blocked in pachytene stage.Interestingly,the depletion of MFN2 did not alter the number of SSCs,rather affect the formation of spermatocytes during spermatogenesis.In addition,when monitoring mitochondrial functions,higher levels of reactive oxygen species(ROS)were detected in MFN2-depleted germ cells,which likely in turn resulted in apoptosis,and finally caused the failure of spermatogenesis.In summary,we revealed essential roles for MFNs in spermatogenesis,and provided important evidence for MFNs-mediated mitochondrial fusion in male reproduction.