title: Rad9a is required for spermatogonia differentiation in mice.
abstract: Spermatogenesis in testes requires precise spermatogonia differentiation. Spermatocytes lacking the Rad9a gene are arrested in pachytene prophase, implying a possible role for RAD9A in spermatogonia differentiation. However, numerous RAD9A-positive pachytene spermatocytes are still observed in mouse testes following Rad9a excision using the Stra8-Cre system, and it is unclear whether Rad9a deletion in spermatogonia interrupts differentiation. Here, we generated a mouse model in which Rad9a was specifically deleted in spermatogonial stem cells (SSCs) using Cre recombinase expression driven by the germ cell-specific Vasa promoter. Adult Rad9a-null male mice were infertile as a result of completely blocked spermatogonia differentiation. No early spermatocytes were detected in mutant testicular cords of 9-day-old mice. Mutant spermatogonia were prone to apoptosis, although proliferation rates were unaffected. Rad9a deletion also resulted in malformation of seminiferous tubules, in which cells assembled irregularly into clusters, and malformation led to testicular cord disruption. Our findings suggest that Rad9a is indispensable for spermatogonia differentiation and testicular development in mice.
authors.affiliation: Key Laboratory of Major Obstetrics Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Hospital Affiliated to Guangzhou Medical University, Guangdong, China.|State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Zhen-Bo
authors.initials: ZB
authors.lastname: Wang
authors.affiliation: Key Laboratory of Major Obstetrics Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Hospital Affiliated to Guangzhou Medical University, Guangdong, China.
authors.forename: Shu-Tao
authors.initials: ST
authors.lastname: Qi
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Xue-Shan
authors.initials: XS
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.|University of the Chinese Academy of Sciences, Beijing, China.
authors.forename: Qiu-Xia
authors.initials: QX
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Guo
authors.initials: G
authors.lastname: Lei
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Tie-Gang
authors.initials: TG
authors.lastname: Meng
authors.affiliation: Key Laboratory of Major Obstetrics Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Hospital Affiliated to Guangzhou Medical University, Guangdong, China.
authors.forename: Li-Feng
authors.initials: LF
authors.lastname: Liang
authors.affiliation: Key Laboratory of Major Obstetrics Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Hospital Affiliated to Guangzhou Medical University, Guangdong, China.
authors.forename: Ye-Xin
authors.initials: YX
authors.lastname: Xian
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Key Laboratory of Major Obstetrics Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Hospital Affiliated to Guangzhou Medical University, Guangdong, China.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Biomembrane, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Major Obstetrics Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Hospital Affiliated to Guangzhou Medical University, Guangdong, China.|Houston Fertility Institute/Houston Fertility Laboratory, Houston, Texas, USA.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.|University of the Chinese Academy of Sciences, Beijing, China.
authors.forename: Qing-Yuan
authors.initials: QY
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000502:physiology*; D002454:Cell Differentiation; D053487:DEAD-box RNA Helicases / Q000032:analysis; D004268:DNA-Binding Proteins / Q000032:analysis; D007248:Infertility, Male / Q000209:etiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D013093:Spermatogonia / Q000166:cytology*; D014157:Transcription Factors / Q000032:analysis
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C509167:Sall4 protein, mouse; D014157:Transcription Factors; C069930:rad9 protein; C090864:Ddx4 protein, mouse; D053487:DEAD-box RNA Helicases
keywords: RAD9A; Sertoli cells; Vasa; differentiation; spermatogenesis