title: Deficiency of Mkrn2 causes abnormal spermiogenesis and spermiation, and impairs male fertility.
abstract: Although recent studies have shed insights on some of the potential causes of male infertility, new underlining molecular mechanisms still remain to be elucidated. Makorin-2 (Mkrn2) is an evolutionarily conserved gene whose biological functions are not fully known. We developed an Mrkn2 knockout mouse model to study the role of this gene, and found that deletion of Mkrn2 in mice led to male infertility. Mkrn2 knockout mice produced abnormal sperms characterized by low number, poor motility, and aberrant morphology. Disruption of Mkrn2 also caused failure of sperm release (spermiation failure) and misarrangement of ectoplasmic specialization (ES) in testes, thus impairing spermiogenesis and spermiation. To understand the molecular mechanism, we found that expression of Odf2, a vital protein in spermatogenesis, was significantly decreased. In addition, we found that expression levels of Odf2 were decreased in Mkrn2 knockout mice. We also found that MKRN2 was prominently expressed in the sperm of normal men, but was significantly reduced in infertile men. This result indicates that our finding is clinically relevant. The results of our study provided insights into a new mechanism of male infertility caused by the MKRN2 downregulation.
authors.affiliation: State Key Laboratory of Reproductive Medicine,Nanjing Medical University, Nanjing, Jiangsu 210029, China.|Department of Pathology, and Cancer Center, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Qian
authors.affiliation: Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Henan 450052, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Reproductive Medicine,Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Reproductive Medicine,Nanjing Medical University, Nanjing, Jiangsu 210029, China.|Department of Pathology, and Cancer Center, Nanjing Medical University, Nanjing, Jiangsu 210029, China.|Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Zhu-Mei
authors.initials: ZM
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Reproductive Medicine,Nanjing Medical University, Nanjing, Jiangsu 210029, China.|Department of Pathology, and Cancer Center, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Ge
authors.affiliation: State Key Laboratory of Reproductive Medicine,Nanjing Medical University, Nanjing, Jiangsu 210029, China.|Department of Pathology, and Cancer Center, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Cheng-Fei
authors.initials: CF
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Reproductive Medicine,Nanjing Medical University, Nanjing, Jiangsu 210029, China.|Department of Pathology, and Cancer Center, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Ying-Chen
authors.initials: YC
authors.lastname: Qian
authors.affiliation: State Key Laboratory of Reproductive Medicine,Nanjing Medical University, Nanjing, Jiangsu 210029, China.|Department of Pathology, and Cancer Center, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Li
authors.affiliation: State Key Laboratory of Reproductive Medicine,Nanjing Medical University, Nanjing, Jiangsu 210029, China.|Department of Pathology, and Cancer Center, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: State Key Laboratory of Reproductive Medicine,Nanjing Medical University, Nanjing, Jiangsu 210029, China.|Department of Pathology, and Cancer Center, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Reproductive Medicine,Nanjing Medical University, Nanjing, Jiangsu 210029, China.|Department of Pathology, and Cancer Center, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yin
authors.affiliation: State Key Laboratory of Reproductive Medicine,Nanjing Medical University, Nanjing, Jiangsu 210029, China.|Department of Pathology, and Cancer Center, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Ji-Tai
authors.initials: JT
authors.lastname: Zheng
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Reproductive Medicine,Nanjing Medical University, Nanjing, Jiangsu 210029, China.|Department of Pathology, and Cancer Center, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Reproductive Medicine,Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Xue-Jiang
authors.initials: XJ
authors.lastname: Guo
authors.affiliation: Center for Molecular Carcinogenesis, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: He
authors.affiliation: Biomedical Engineer Research Center, Kunming Medical University, Kunming, Yunnan 65000, China.
authors.forename: Marie
authors.initials: M
authors.lastname: Lin
authors.affiliation: Center for Molecular Carcinogenesis, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Ling-Zhi
authors.initials: LZ
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Reproductive Medicine,Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Jia-Hao
authors.initials: JH
authors.lastname: Sha
authors.affiliation: State Key Laboratory of Reproductive Medicine,Nanjing Medical University, Nanjing, Jiangsu 210029, China.|Department of Pathology, and Cancer Center, Nanjing Medical University, Nanjing, Jiangsu 210029, China.|Center for Molecular Carcinogenesis, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Bing-Hua
authors.initials: BH
authors.lastname: Jiang
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D007248:Infertility, Male; D008297:Male; D018345:Mice, Knockout; D012261:Ribonucleoproteins / Q000172:deficiency*; D013091:Spermatogenesis; D013094:Spermatozoa / Q000166:cytology / Q000502:physiology
chemical_list: D006360:Heat-Shock Proteins; C512678:Mkrn2 protein, mouse; C490106:Odf2 protein, mouse; D012261:Ribonucleoproteins