Deficiency of MFSD6L, an acrosome membrane protein, causes oligoasthenoteratozoospermia in humans and mice  

作　　者：Dapeng Zhou Huan Wu Lingbo Wang Xuemei Wang Shuyan Tang Yiling Zhou Jiaxiong Wang Bangguo Wu Jianan Tang Xuehai Zhou Shixiong Tian Shuang Liu Mingrong Lv Xiaojin He Li Jin Hujuan Shi Feng Zhang Yunxia Cao Chunyu Liu 

机构地区：[1]State Key Laboratoyf Genetic Engineering,Human Phenome Insttute,Zhangjiang Fudan Interational Innovation Center,Fudan University,Shanghai 200438,China [2]Institute of Medical Genetics and Genomics,Obstetrics and Gynecology Hospital,Fudan University,Shanghai 200011,China [3]Reproductive Medicine Center,Department of Obstetrics and Gynecology,The First Affiliated Hospital of Anhui Medical University,Hefei,Anhui 230022,China [4]NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract,Anhui Medical University,Hefei,Anhui 230032,China [5]Key Laboratory of Population Health Across Life Cycle,Anhui Medical University,Ministry of Education of the People's Republic of China,Hefei,Anhui 230032,China [6]Shanghai Key Laboratory of Metabolic Remodeling and Health,Institute of Metabolism and Integrative Biology,Institute of Reproduction and Development,Obstetrics andGynecologyHospital,Fudan University,Shanghai 200433,China [7]Shanghai-MOST Key Laboratory of Health and Disease Genomics,NHC Key Lab of Reproduction Regulation,Shanghai Institute for Biomedical and Pharmaceutical Technologies,School of Pharmacy,Fudan University,Shanghai 200237,China [8]State Key Laboratory of Reproductive Medicine,The Affiliated Suzhou Hospitalof Nanjing Medical University,Suzhou,Jiangsu 2002,China [9]Suzhou Municipal Hospital,Suzhou,Jiangsu 215002,China [10]Reproductive Medicine Center,Department of Obstetrics and Gynecology,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200080,China [11]Shanghai Key Laboratory of Embryo Original Diseases,Soong Ching Ling Institute of Maternity and Child Health,International Peace Maternity and Child Health Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200030,China

出　　处：《Journal of Genetics and Genomics》2024年第10期1007-1019,共13页遗传学报（英文版）

基　　金：This study was supported by the National Key Research and Development Program of China(2021YFC2701400 and 2023YFC2705600);the National Natural Science Foundation of China(32288101,32100480,32370654,82271639,32322017,and32200485).

摘　　要：Oligoasthenoteratozoospermia is an important factor affecting male fertility and has been found to be associated with genetic factors.However,there are stll a proportion of oligoasthenoteratozoospermia cases that cannot be explained by known pathogenic genetic variants.Here,we perform genetic analyses and identify bi-allelic loss-of-function variants of MFSD6L from an oligoasthenoteratozoospermia-affected family.Mfsd6l knock-out male mice also present male subfertility with reduced sperm concentration,motility,and deformed acrosomes.Further mechanistic analyses reveal that MFsD6L,as an acrosome membrane protein,plays an important role in the formation of acrosome by interacting with the inner acrosomal membrane protein SPACA1.Moreover,poor embryonic development is consistently observed after intracytoplasmic sperm injection treatment using spermatozoa from the MFSD6L-deficient man and male mice.Collectively,our findings reveal that MFSD6L is required for the anchoring of sperm acrosome and head shaping.The deficiency of MFsD6L affects male fertility and causes oligoasthenoter-atozoospermia in humans and mice.

关 键 词：Male fertility OLIGOASTHENOTERATOZOOSPERMIA MFSD6L ACROSOME ICSI 

分 类 号：R698.2[医药卫生—泌尿科学]