Infertility is a global health issue that affects 1 in 6 couples, with male factors contributing to 50% of cases. The flagellar axoneme is a motility apparatus of spermatozoa, and disruption of its structure or function could lead to male infertility. The axoneme consists of a "9+2" structure that contains a central pair of two singlet microtubules surrounded by nine doublet microtubules, in addition to several macromolecular complexes such as dynein arms, radial spokes, and nexin-dynein regulatory complexes. Molecular components of the flagellar axoneme are evolutionally conserved from unicellular flagellates to mammals, including mice. Although knockout (KO) mice have been generated to understand their function in the formation and motility regulation of sperm flagella, the majority of KO mice die before sexual maturation due to impaired ciliary motility, which makes it challenging to analyze mature spermatozoa. In this review, we introduce methods that have been used to overcome premature lethality, focusing on KO mouse lines of central pair components.
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http://dx.doi.org/10.1538/expanim.20-0064 | DOI Listing |
Andrology
January 2025
Institute for Advanced Biosciences, Team Genetics Epigenetics and Therapies of Infertility, University of Grenoble Alpes, Grenoble, France.
Background: Asthenozoospermia, characterized by reduced sperm motility, is a common cause of male infertility. Multiple morphological abnormalities of the sperm flagella (MMAF) represent a severe and genetically heterogeneous form of asthenozoospermia. Over 50 genes have been associated, but approximately half of MMAF cases remain unexplained.
View Article and Find Full Text PDFSci China Life Sci
December 2024
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.
Asthenoteratozoospermia is a common cause of male infertility. To further define the genetic causes underlying asthenoteratozoospermia, we performed whole-exome sequencing in a cohort of Han Chinese men with asthenoteratozoospermia. Homozygous deleterious variants of MYCBPAP were first identified in two unrelated Chinese cases.
View Article and Find Full Text PDFAsian J Androl
December 2024
Institute of Health and Medicine, Hefei Comprehensive National Science Center, Center for Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China, Hefei 230027, China.
Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella (MMAF). Distinct projections encircling the central microtubules of the spermatozoal axoneme play pivotal roles in flagellar bending and spermatozoal movement. Mammalian sperm-associated antigen 17 (SPAG17) encodes a conserved axonemal protein of cilia and flagella, forming part of the C1a projection of the central apparatus, with functions related to ciliary/flagellar motility, skeletal growth, and male fertility.
View Article and Find Full Text PDFBasic Clin Androl
December 2024
Institute for Advanced Biosciences, INSERM U 1209, CNRS UMR 5309, Université Grenoble Alpes, Team 'Physiopathology and Pathophysiology of Sperm cells', 38000, Grenoble, France.
The annulus is an electron-dense ring structure that surrounds the axoneme and compartmentalizes the sperm flagellum into two parts: the midpiece and the principal piece. The function of the annulus as a diffusion barrier in the mature spermatozoon is now well described but its function during spermiogenesis remains unclear. The intriguing spatio-temporal dynamics of the annulus during spermiogenesis and its position at the interface of the two main flagellar compartments have been highlighted for more than 50 years, and suggest a major role in this process.
View Article and Find Full Text PDFElife
December 2024
Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
The structural integrity of the sperm is crucial for male fertility, defects in sperm head-tail linkage and flagellar axoneme are associated with acephalic spermatozoa syndrome (ASS) and the multiple morphological abnormalities of the sperm flagella (MMAF). Notably, impaired head-tail coupling apparatus (HTCA) often accompanies defects in the flagellum structure, however, the molecular mechanisms underlying this phenomenon remain elusive. Here, we identified an evolutionarily conserved coiled-coil domain-containing (CCDC) protein, CCDC113, and found the disruption of CCDC113 produced spermatozoa with disorganized sperm flagella and HTCA, which caused male infertility.
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