sperm flagellum
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2022 ◽  
Author(s):  
Ruidan Zhang ◽  
Wei Li ◽  
Li Yuan ◽  
Fei Gao ◽  
Bingbing Wu ◽  
...  

Sperm flagellum is essential for male fertility, defects in flagellum biogenesis are associated with male infertility. Deficiency of CCDC42 is associated with malformation of the mouse sperm flagella. Here, we find that the testis-specific expressed protein CCDC38 (coiled coil domain containing 38) interacts with CCDC42 and localizes on manchette and sperm tail during spermiogenesis. Inactivation of CCDC38 in male mice results in distorted manchette, multiple morphological abnormalities of the flagella (MMAF) of spermatozoa, and eventually male sterility. Furthermore, we find that CCDC38 interacts with intra-flagellar transport protein 88 (IFT88) as well as the outer dense fibrous 2 (ODF2), and its depletion reduces the transportation of ODF2 to flagellum. Altogether, our results uncover the essential role of CCDC38 during sperm flagellum biogenesis, and suggesting the defects of these genes might be associated with male infertility in human being.


Development ◽  
2021 ◽  
Author(s):  
Siyu Liu ◽  
Jintao Zhang ◽  
Zine Eddine Kherraf ◽  
Shuya Sun ◽  
Xin Zhang ◽  
...  

Defects in the structure or motility of cilia and flagella may lead to severe diseases such as primary ciliary dyskinesia (PCD), a multisystemic disorder with heterogeneous manifestations affecting primarily respiratory and reproductive functions. We report that CFAP61 is a conserved component of the Calmodulin and radial Spoke associated Complex (CSC) of cilia. We find that a CFAP61 splice variant, c.143+5G>A, causes exon skipping/ intron retention in human, inducing a multiple morphological abnormalities of the flagella (MMAF) phenotype. We generated Cfap61 knockout mice that recapitulate the infertility phenotype of the human CFAP61 mutation, but without other symptoms usually observed in PCD. We find that CFAP61 interacts with the CSC, radial spoke (RS) stalk and head. During early stages of Cfap61−/- spermatid development, the assembly of RS components is impaired. With the progress of spermiogenesis, the axoneme in Cfap61−/- cells becomes unstable and scatters, and the distribution of intraflagellar transport proteins is disrupted. This study reveals an organ specific mechanism of axoneme stabilization that is related to male infertility.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Qian Ma ◽  
Congcong Cao ◽  
Changshui Zhuang ◽  
Xiaomin Luo ◽  
Xiaofeng Li ◽  
...  

AbstractSpermiogenesis is a complex process depending on the sophisticated coordination of a myriad of testis-enriched gene regulations. The regulatory pathways that coordinate this process are not well understood, and we demonstrate here that AXDND1, as a novel testis-enriched gene is essential for spermiogenesis and male fertility. AXDND1 is exclusively expressed in the round and elongating spermatids in humans and mice. We identified two potentially deleterious mutations of AXDND1 unique to non‐obstructive azoospermia (NOA) patients through selected exonic sequencing. Importantly, Axdnd1 knockout males are sterile with reduced testis size caused by increased germ cell apoptosis and sloughing, exhibiting phenotypes consistent with oligoasthenoteratozoospermia. Axdnd1 mutated late spermatids showed head deformation, outer doublet microtubules deficiency in the axoneme, and loss of corresponding accessory structures, including outer dense fiber (ODF) and mitochondria sheath. These phenotypes were probably due to the perturbed behavior of the manchette, a dynamic structure where AXDND1 was localized. Our findings establish AXDND1 as a novel testis-enrich gene essential for spermiogenesis and male fertility probably by regulating the manchette dynamics, spermatid head shaping, sperm flagellum assembly.


2021 ◽  
Vol 22 (17) ◽  
pp. 9104
Author(s):  
Masahiro Naruse ◽  
Midori Matsumoto

In echinoderms, sperm swims in random circles and turns in response to a chemoattractant. The chemoattractant evokes transient Ca2+ influx in the sperm flagellum and induces turning behavior. Recently, the molecular mechanisms and biophysical properties of this sperm response have been clarified. Based on these experimental findings, in this study, we reconstructed a sperm model in silico to demonstrate an algorithm for sperm chemotaxis. We also focused on the importance of desensitizing the chemoattractant receptor in long-range chemotaxis because sperm approach distantly located eggs, and they must sense the chemoattractant concentration over a broad range. Using parameters of the sea urchin, simulations showed that a number of sperm could reach the egg from millimeter-order distances with desensitization, indicating that we could organize a functional sperm model, and that desensitization of the receptor is essential for sperm chemotaxis. Then, we compared the model with starfish sperm, which has a different desensitization scheme and analyzed the properties of the model against various disturbances. Our approach can be applied as a novel tool in chemotaxis research.


Author(s):  
Eamonn A. Gaffney ◽  
Kenta Ishimoto ◽  
Benjamin J. Walker

In one of the first examples of how mechanics can inform axonemal mechanism, Machin's study in the 1950s highlighted that observations of sperm motility cannot be explained by molecular motors in the cell membrane, but would instead require motors distributed along the flagellum. Ever since, mechanics and hydrodynamics have been recognised as important in explaining the dynamics, regulation, and guidance of sperm. More recently, the digitisation of sperm videomicroscopy, coupled with numerous modelling and methodological advances, has been bringing forth a new era of scientific discovery in this field. In this review, we survey these advances before highlighting the opportunities that have been generated for both recent research and the development of further open questions, in terms of the detailed characterisation of the sperm flagellum beat and its mechanics, together with the associated impact on cell behaviour. In particular, diverse examples are explored within this theme, ranging from how collective behaviours emerge from individual cell responses, including how these responses are impacted by the local microenvironment, to the integration of separate advances in the fields of flagellar analysis and flagellar mechanics.


2021 ◽  
Author(s):  
Yanhe Zhao ◽  
Huafeng Wang ◽  
Caroline Wiesehoefer ◽  
Naman B Shah ◽  
Evan Reetz ◽  
...  

The sperm calcium channel CatSper plays a central role in successful fertilization as a primary Ca2+ gateway into the sperm flagellum. However, the complex subunit composition of CatSper has impeded its reconstitution in vitro and structural elucidation. Here, we applied cryo-electron tomography to visualize the macromolecular organization of the native CatSper channel complex in intact mammalian sperm, as well as identified three additional CatSper-associated proteins. The repeating CatSper units form long zigzag-rows in four nanodomains along the flagella. In both mouse and human sperm, each CatSper repeat consists of a tetrameric pore complex. Murine CatSper contains an additional outwardly directed wing-structure connected to the tetrameric channel. The majority of the extracellular domains form a canopy above each pore-forming channel that interconnects to a zigzag-shaped roof. The intracellular domains link two neighboring channel complexes to a diagonal array. The loss of this intracellular link in Efcab9-/- sperm distorts the longitudinally aligned zigzag pattern and compromises flagellar movement. This work offers unique insights into the mechanisms underlying the assembly and transport of the CatSper complex to generate the nanodomains and provides a long-sought structural basis for understanding CatSper function in the regulation of sperm motility.


Author(s):  
Bingbing Wu ◽  
Xiaochen Yu ◽  
Chao Liu ◽  
Lina Wang ◽  
Tao Huang ◽  
...  

The sperm flagellum is essential for male fertility. Despite vigorous research progress toward understanding the pathogenesis of flagellum-related diseases, much remains unknown about the mechanisms underlying the flagellum biogenesis itself. Here, we show that the cilia and flagella associated protein 53 (Cfap53) gene is predominantly expressed in testes, and it is essential for sperm flagellum biogenesis. The knockout of this gene resulted in complete infertility in male mice but not in the females. CFAP53 localized to the manchette and sperm tail during spermiogenesis, the knockout of this gene impaired flagellum biogenesis. Furthermore, we identified two manchette and sperm tail-associated proteins that interacted with CFAP53 during spermiogenesis. Together, our results suggest that CFAP53 is an essential protein for sperm flagellum biogenesis, and its mutations might be associated with multiple morphological abnormalities of the flagella (MMAF).


2021 ◽  
Author(s):  
Siyu Liu ◽  
Jintao Zhang ◽  
Zine Eddine Kherraf ◽  
Shuya Sun ◽  
Xin Zhang ◽  
...  

Defects in the structure or motility of cilia and flagella may lead to severe diseases such as primary ciliary dyskinesia (PCD), a multisystemic disorder with heterogeneous manifestations affecting primarily respiratory and reproductive functions. We report that CFAP61 is a conserved component of the Calmodulin and radial Spoke associated Complex (CSC) of cilia. We find that a CFAP61 splice variant, c.143+5G>A, causes exon skipping in human, inducing a multiple morphological abnormalities of the flagella (MMAF) phenotype. We generated Cfap61 knockout mice that recapitulate the infertility phenotype of the human CFAP61 mutation, but without other symptoms usually observed in PCD. We find that CFAP61 interacts with the CSC, radial spoke stalk and RS head. During early stages of Cfap61-/- spermatid development, the assembly of RS components is impaired. With the progress of spermiogenesis, the axoneme in Cfap61-/- cells becomes unstable and scatters, and the distribution of intraflagellar transport proteins is disrupted.


2021 ◽  
Author(s):  
Bingbing Wu ◽  
Xiaochen Yu ◽  
Chao Liu ◽  
Lina Wang ◽  
Tao Huang ◽  
...  

AbstractThe sperm flagellum is essential for male fertility. Despite vigorous research progress towards understanding the pathogenesis of flagellum-related diseases, much remains unknown about the mechanisms underlying the flagellum biogenesis itself. Here, we show that the cilia and flagella associated protein 53 (Cfap53) gene is predominantly expressed in testes, and it is essential for sperm flagellum biogenesis. The knockout of this gene resulted in complete infertility in male mice but not in the females. CFAP53 localized to the manchette and sperm tail during spermiogenesis, the knockout of this gene impaired flagellum biogenesis. Furthermore, we identified two manchette and sperm tail-associated proteins that interacted with CFAP53 during spermiogenesis. The disruption of Cfap53 decreased the expression level of these two proteins and disrupted their localization in spermatids. Together, our results suggest that CFAP53 is an essential protein for sperm flagellum biogenesis, and its mutations might be associated with MMAF.


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