CCDC38 is required for sperm flagellum biogenesis and male fertility in mice. 2022

Ruidan Zhang, and Bingbing Wu, and Chao Liu, and Zhe Zhang, and Xiuge Wang, and Liying Wang, and Sai Xiao, and Yinghong Chen, and Huafang Wei, and Hui Jiang, and Fei Gao, and Li Yuan, and Wei Li
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Stem Cell and Regenerative Medicine Innovation Institute, Chinese Academy of Sciences, Beijing 100101, China.

The sperm flagellum is essential for male fertility, and defects in flagellum biogenesis are associated with male infertility. Deficiency of coiled-coil domain-containing (CCDC) 42 (CCDC42) is specifically associated with malformation of mouse sperm flagella. Here, we find that the testis-specific protein CCDC38 interacts with CCDC42, localizing on the manchette and sperm tail during spermiogenesis. Inactivation of CCDC38 in male mice results in a distorted manchette, multiple morphological abnormalities of the flagella of spermatozoa and eventually male sterility. Furthermore, we find that CCDC38 interacts with intraflagellar transport protein 88 (IFT88), as well as outer dense fibrous 2 (ODF2), and the knockout of Ccdc38 reduces transport of ODF2 to the flagellum. Altogether, our results uncover the essential role of CCDC38 in sperm flagellum biogenesis, and suggest that some mutations of these genes might be associated with male infertility in humans.

UI MeSH Term Description Entries
D007248 Infertility, Male The inability of the male to effect FERTILIZATION of an OVUM after a specified period of unprotected intercourse. Male sterility is permanent infertility. Sterility, Male,Sub-Fertility, Male,Subfertility, Male,Male Infertility,Male Sterility,Male Sub-Fertility,Male Subfertility,Sub Fertility, Male
D008297 Male Males
D005298 Fertility The capacity to conceive or to induce conception. It may refer to either the male or female. Fecundity,Below Replacement Fertility,Differential Fertility,Fecundability,Fertility Determinants,Fertility Incentives,Fertility Preferences,Fertility, Below Replacement,Marital Fertility,Natural Fertility,Subfecundity,World Fertility Survey,Determinant, Fertility,Determinants, Fertility,Fertility Determinant,Fertility Incentive,Fertility Preference,Fertility Survey, World,Fertility Surveys, World,Fertility, Differential,Fertility, Marital,Fertility, Natural,Preference, Fertility,Preferences, Fertility,Survey, World Fertility,Surveys, World Fertility,World Fertility Surveys
D006360 Heat-Shock Proteins Proteins which are synthesized in eukaryotic organisms and bacteria in response to hyperthermia and other environmental stresses. They increase thermal tolerance and perform functions essential to cell survival under these conditions. Stress Protein,Stress Proteins,Heat-Shock Protein,Heat Shock Protein,Heat Shock Proteins,Protein, Stress
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013082 Sperm Tail The posterior filiform portion of the spermatozoon (SPERMATOZOA) that provides sperm motility. Sperm Flagellum,Flagellum, Sperm,Flagellums, Sperm,Sperm Flagellums,Sperm Tails,Tail, Sperm,Tails, Sperm
D013094 Spermatozoa Mature male germ cells derived from SPERMATIDS. As spermatids move toward the lumen of the SEMINIFEROUS TUBULES, they undergo extensive structural changes including the loss of cytoplasm, condensation of CHROMATIN into the SPERM HEAD, formation of the ACROSOME cap, the SPERM MIDPIECE and the SPERM TAIL that provides motility. Sperm,Spermatozoon,X-Bearing Sperm,X-Chromosome-Bearing Sperm,Y-Bearing Sperm,Y-Chromosome-Bearing Sperm,Sperm, X-Bearing,Sperm, X-Chromosome-Bearing,Sperm, Y-Bearing,Sperm, Y-Chromosome-Bearing,Sperms, X-Bearing,Sperms, X-Chromosome-Bearing,Sperms, Y-Bearing,Sperms, Y-Chromosome-Bearing,X Bearing Sperm,X Chromosome Bearing Sperm,X-Bearing Sperms,X-Chromosome-Bearing Sperms,Y Bearing Sperm,Y Chromosome Bearing Sperm,Y-Bearing Sperms,Y-Chromosome-Bearing Sperms
D013737 Testis The male gonad containing two functional parts: the SEMINIFEROUS TUBULES for the production and transport of male germ cells (SPERMATOGENESIS) and the interstitial compartment containing LEYDIG CELLS that produce ANDROGENS. Testicles,Testes,Testicle
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018345 Mice, Knockout Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes. Knockout Mice,Mice, Knock-out,Mouse, Knockout,Knock-out Mice,Knockout Mouse,Mice, Knock out

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