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

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外文摘要：Oligoasthenoteratozoospermia is an important factor affecting male fertility and has been found to be associated with genetic factors.However,there are still 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.

外文关键词：

Male fertilityOligoasthenoteratozoospermiaMFSD6LAcrosomeICSI

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、Huijuan Shi、Feng Zhang、Yunxia Cao、Chunyu Liu

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作者单位：

State Key Laboratory of Genetic Engineering,Human Phenome Institute,Zhangjiang Fudan International Innovation Center,Fudan University,Shanghai 200438,China

Institute of Medical Genetics and Genomics,Obstetrics and Gynecology Hospital,Fudan University,Shanghai 200011,China

Reproductive Medicine Center,Department of Obstetrics and Gynecology,The First Affiliated Hospital of Anhui Medical University,Hefei,Anhui 230022,China

NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract,Anhui Medical University,Hefei,Anhui 230032,China

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

Shanghai Key Laboratory of Metabolic Remodeling and Health,Institute of Metabolism and Integrative Biology,Institute of Reproduction and Development,Obstetrics and Gynecology Hospital,Fudan University,Shanghai 200433,China

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

State Key Laboratory of Reproductive Medicine,The Affiliated Suzhou Hospital of Nanjing Medical University,Suzhou,Jiangsu 215002,China

Suzhou Municipal Hospital,Suzhou,Jiangsu 215002,China

Reproductive Medicine Center,Department of Obstetrics and Gynecology,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200080,China

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

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基金：

National Key Research and Development Program of ChinaNational Key Research and Development Program of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of China

项目编号：

2021YFC27014002023YFC2705600322881013210048032370654822716393232201732200485

出版年：

2024

DOI：

10.1016/j.jgg.2024.06.008

遗传学报

中国遗传学会中国科学院遗传与发育生物学研究所

遗传学报

CSTPCD

影响因子：0.821

ISSN：1673-8527

年,卷(期)：2024.51(10)