| With the increasing pressure of life,the incidence rate of male infertility has increased significantly.We found a new pathogenic gene pias4 in a relative family of azoospermia phenotype,and a dnah7 gene mutation with high correlation with the disease phenotype in two asthenospermia patients with PCD symptoms.We found a pair of inbred brothers with a homozygous mutation of pias4 gene,showing a typical azoospermic phenotype.Moreover,the expression of pias4 protein in testis of patients with pias4 gene mutation was significantly down regulated.After knockdown of pias4 protein in mouse spermatogonial cell line gc-lspg,apoptosis increased and growth curve was affected,indicating that pias4 gene is closely related to spermatogonia proliferation.Our results show that it is very likely that the mutation of pias4 gene will affect the proliferation of spermatogonia,and the process of spermatogenesis will not be normal.Finally,we successfully constructed pias4 knockout mice,and further study the function of pias4 gene in spermatogenesis in the future.Dynein arm proteins play an important role in the regulation of cilia/sperm flagellum movement.These protein defects damage ciliary movement and lead to the phenotype of primary ciliary movement disorder(PCD).However,little is known about the effect of dynein arm protein deficiency on sperm flagellum function.Here,we found that two asthenospermia patients with PCD symptoms carry three new mutations of dnah7 gene.The mutation of dnah7 resulted in the decrease of dnah7 protein level in spermatozoa,which showed the loss of specific inner dynein arm and no other axon defects.The ICSI treatment of patient 2(P2)showed that the quality of sperm nucleus was good.Our findings indicate that dnah7 gene mutation not only causes symptoms of PCD,but also affects sperm motility and causes asthenospermia phenotype,which provides a new way for the diagnosis and treatment of infertility phenotype in PCD patients. |
PDF Full Text Request