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

Dapeng Zhou ¹Huan Wu ²Lingbo Wang ³Xuemei Wang ⁴Shuyan Tang ⁵Yiling Zhou ⁵Jiaxiong Wang ⁶Bangguo Wu ³Jianan Tang ⁴Xuehai Zhou ⁴Shixiong Tian ³Shuang Liu ¹Mingrong Lv ²Xiaojin He ⁷Li Jin ⁸Huijuan Shi ⁴Feng Zhang ⁹Yunxia Cao ²Chunyu Liu¹⁰

扫码查看

作者信息

1. 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
2. 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
3. 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
4. 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
5. Institute of Medical Genetics and Genomics,Obstetrics and Gynecology Hospital,Fudan University,Shanghai 200011,China
6. 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
7. Reproductive Medicine Center,Department of Obstetrics and Gynecology,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200080,China
8. State Key Laboratory of Genetic Engineering,Human Phenome Institute,Zhangjiang Fudan International Innovation Center,Fudan University,Shanghai 200438,China
9. 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;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
10. 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
折叠

Abstract

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.

Key words

Male fertility/Oligoasthenoteratozoospermia/MFSD6L/Acrosome/ICSI

引用本文复制引用

基金项目

National Key Research and Development Program of China(2021YFC2701400)

National Key Research and Development Program of China(2023YFC2705600)

National Natural Science Foundation of China(32288101)

National Natural Science Foundation of China(32100480)

National Natural Science Foundation of China(32370654)

National Natural Science Foundation of China(82271639)

National Natural Science Foundation of China(32322017)

National Natural Science Foundation of China(32200485)

出版年

2024

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

段落导航