典型文献
Mutations in CCIN cause teratozoospermia and male infertility
文献摘要：
Teratozoospermia is usually associated with defective spermiogenesis and is a disorder with considerable genetic heterogeneity.Although previous studies have identified several teratozoospermia-associated genes,the etiology remains unknown for a majority of affected men.Here,we identified a homozygous missense mutation and a compound heterozygous mutation of CCIN in patients suffering from terato-zoospermia.CCIN encodes the cytoskeletal protein Calicin that is involved in the formation and mainte-nance of the highly regular organization of the calyx of mammalian spermatozoa,and has been proposed to play a role in sperm head structure remodeling during the process of spermiogenesis.Our morpholog-ical and ultrastructural analyses of the spermatozoa obtained from all three men harboring deleterious CCIN mutants reveal severe head malformation.Further immunofluorescence assays unveil markedly reduced levels of Calicin in spermatozoa.These patient phenotypes are successfully recapitulated in mouse models expressing the disease-associated variants,confirming the role of Calicin in male fertility.Notably,all mutant spermatozoa from mice and human patients fail to adhere to the zona mass,which likely is the major mechanistic reason for CCIN-mutant sperm-derived infertility.Finally,the use of intra-cytoplasmic sperm injections(ICSI)successfully makes mutated mice and two couples with CCIN variants have healthy offspring.Taken together,our findings identify the role of Calicin in sperm head shaping and male fertility,providing important guidance for genetic counseling and assisted reproduction treatments.
文献关键词：
中图分类号：
作者姓名：
Yong Fan;Chenhui Huang;Juan Chen;Yanyan Chen;Yan Wang;Zhiguang Yan;Weina Yu;Haibo Wu;Ying Yang;Leitong Nie;Sijia Huang;Fangfang Wang;Haoyu Wang;Yunfeng Hua;Qifeng Lyu;Yanping Kuang;Ming Lei
作者机构：
Department of Assisted Reproduction,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200011,China;Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200011,China;Shanghai Institute of Precision Medicine,Shanghai 200125,China;National Key Laboratory of Crop Genetic Improvement,Huazhong Agriculture University,Wuhan 430072,China;State Key Laboratory of Oncogenes and Related Genes,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200011,China;Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China
文献出处：
引用格式：
[1]Yong Fan;Chenhui Huang;Juan Chen;Yanyan Chen;Yan Wang;Zhiguang Yan;Weina Yu;Haibo Wu;Ying Yang;Leitong Nie;Sijia Huang;Fangfang Wang;Haoyu Wang;Yunfeng Hua;Qifeng Lyu;Yanping Kuang;Ming Lei-.Mutations in CCIN cause teratozoospermia and male infertility)[J].科学通报（英文版）,2022(20):2112-2123
A类：
CCIN,Teratozoospermia,terato,zoospermia,Calicin
B类：
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AB值：
0.585426
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