首页|Coiled-coil domain-containing 38 is required for acrosome biogenesis and fibrous sheath assembly in mice

Coiled-coil domain-containing 38 is required for acrosome biogenesis and fibrous sheath assembly in mice

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During spermiogenesis,haploid spermatids undergo dramatic morphological changes to form slender sperm flagella and cap-like acrosomes,which are required for successful fertilization.Severe deformities in flagella cause a male infertility syndrome,multiple morphological abnormalities of the flagella(MMAF),while acrosomal hypoplasia in some cases leads to sub-optimal embryonic developmental potential.However,evidence regarding the occurrence of acrosomal hypoplasia in MMAF is limited.Here,we report the generation of base-edited mice knocked out for coiled-coil domain-containing 38(Ccdc38)via inducing a nonsense mutation and find that the males are infertile.The Ccdc38-KO sperm display acrosomal hypo-plasia and typical MMAF phenotypes.We find that the acrosomal membrane is loosely anchored to the nucleus and fibrous sheaths are disorganized in Ccdc38-KO sperm.Further analyses reveal that Ccdc38 knockout causes a decreased level of TEKT3,a protein associated with acrosome biogenesis,in testes and an aberrant distribution of TEKT3 in sperm.We finally show that intracytoplasmic sperm injection over-comes Ccdc38-related infertility.Our study thus reveals a previously unknown role for CCDC38 in acro-some biogenesis and provides additional evidence for the occurrence of acrosomal hypoplasia in MMAF.

Acrosomal hypoplasiaMultiple morphological abnormalities of the flagella(MMAF)InfertilitySperm motilityAsthenoteratozoospermiaDisease modeling

Yaling Wang、Xueying Huang、Guoying Sun、Jingwen Chen、Bangguo Wu、Jiahui Luo、Shuyan Tang、Peng Dai、Feng Zhang、Jinsong Li、Lingbo Wang

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Shanghai Key Laboratory of Metabolic Remodeling and Health,Institute of Metabolism and Integrative Biology,Fudan University,Shanghai 200438,China

Institute of Reproduction and Development,Obstetrics and Gynecology Hospital,Fudan University,Shanghai 200011,China

Shanghai Key Laboratory of Maternal and Fetal Medicine,Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital,Frontier Science Center for Stem Cell Research,School of Life Sciences and Technology,Tongji University,Shanghai 200092,China

State Key Laboratory of Cell Biology,CAS Center for Excellence in Molecular Cell Science,Shanghai Institute of Biochemistry and Cell Biology,Chinese Academy of Sciences,Shanghai 200031,China

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

2021YFC27014003200039332288101

2024

10.1016/j.jgg.2023.09.002

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(4)
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