scholarly journals Essential role of CFAP53 in sperm flagellum biogenesis

2021 ◽  
Author(s):  
Bingbing Wu ◽  
Xiaochen Yu ◽  
Chao Liu ◽  
Lina Wang ◽  
Tao Huang ◽  
...  
Keyword(s):  
Male Fertility ◽  
Essential Role ◽  
Expression Level ◽  
Research Progress ◽  
Male Mice ◽  
Sperm Tail ◽  
Sperm Flagellum ◽  
Associated Proteins ◽  
Cilia And Flagella

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.

scholarly journals Essential Role of CFAP53 in Sperm Flagellum Biogenesis

2021 ◽  
Vol 9 ◽  
Author(s):  
Bingbing Wu ◽  
Xiaochen Yu ◽  
Chao Liu ◽  
Lina Wang ◽  
Tao Huang ◽  
...  
Keyword(s):  
Male Fertility ◽  
Essential Role ◽  
Research Progress ◽  
Male Mice ◽  
Sperm Tail ◽  
Morphological Abnormalities ◽  
Sperm Flagellum ◽  
Associated Proteins ◽  
Cilia And Flagella

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).

scholarly journals Ccdc38 is required for sperm flagellum biogenesis and male fertility in mouse

2022 ◽  
Author(s):  
Ruidan Zhang ◽  
Wei Li ◽  
Li Yuan ◽  
Fei Gao ◽  
Bingbing Wu ◽  
...  
Keyword(s):  
Male Infertility ◽  
Male Fertility ◽  
Essential Role ◽  
Coiled Coil ◽  
Male Mice ◽  
Sperm Tail ◽  
Mouse Sperm ◽  
Sperm Flagellum ◽  
Coiled Coil Domain

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.

scholarly journals Essential Role of the p110β Subunit of Phosphoinositide 3-OH Kinase in Male Fertility

2010 ◽  
Vol 21 (5) ◽  
pp. 704-711 ◽  
Author(s):  
Elisa Ciraolo ◽  
Fulvio Morello ◽  
Robin M. Hobbs ◽  
Frieder Wolf ◽  
Romina Marone ◽  
...  
Keyword(s):  
Male Fertility ◽  
Essential Role ◽  
Spermatogenic Cells ◽  
Male Mice ◽  
Catalytic Subunits ◽  
Adult Testis ◽  
New Treatments ◽  
The Way

Phosphoinositide 3-kinases (PI3K) are key molecular players in male fertility. However, the specific roles of different p110 PI3K catalytic subunits within the spermatogenic lineage have not been characterized so far. Herein, we report that male mice expressing a catalytically inactive p110β develop testicular hypotrophy and impaired spermatogenesis, leading to a phenotype of oligo-azoospermia and defective fertility. The examination of testes from p110β-defective tubules demonstrates a widespread loss in spermatogenic cells, due to defective proliferation and survival of pre- and postmeiotic cells. In particular, p110β is crucially needed in c-Kit–mediated spermatogonial expansion, as c-Kit–positive cells are lost in the adult testis and activation of Akt by SCF is blocked by a p110β inhibitor. These data establish that activation of the p110β PI3K isoform by c-Kit is required during spermatogenesis, thus opening the way to new treatments for c-Kit positive testicular cancers.

scholarly journals Wampa is a dynein subunit required for axonemal assembly and male fertility in Drosophila

2019 ◽  
Author(s):  
Elisabeth Bauerly ◽  
Kexi Yi ◽  
Matthew C. Gibson
Keyword(s):  
Male Fertility ◽  
Primary Ciliary Dyskinesia ◽  
Functional Role ◽  
Essential Role ◽  
Respiratory Infections ◽  
Pathological Features ◽  
Dynein Arms ◽  
Cilia And Flagella ◽  
Ciliary Dyskinesia

AbstractAxonemal dyneins are motor proteins that form the inner and outer arms of the axoneme in cilia and flagella. Defects in dynein arms are the leading cause of primary ciliary dyskinesia (PCD), which is characterized by chronic respiratory infections, situs inversus, and sterility. Despite current understanding of pathological features associated with PCD, many of their causative genes still remain elusive. Here we analyze genetic requirements for wampa (wam), a previously uncharacterized component of the outer dynein arm that is essential for male fertility. In addition to a role in outer dynein arm formation, we uncovered additional requirements during spermatogenesis, including regulation of remodeling events for the mitochondria and the nucleus. Due to the conserved nature of axonemal dyneins and their essential role in both PCD and fertility, this study advances our understanding of the pathology of PCD, as well as the functional role of dyneins in axonemal formation and spermatogenesis.

scholarly journals Kindlin-2 in Sertoli cells is essential for testis development and male fertility in mice

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Xiaochun Chi ◽  
Weiwei Luo ◽  
Jiagui Song ◽  
Bing Li ◽  
Tiantian Su ◽  
...  
Keyword(s):  
Sertoli Cells ◽  
Male Fertility ◽  
Nuclear Translocation ◽  
Hippo Pathway ◽  
Reproductive Organs ◽  
Male Reproduction ◽  
Barrier Structure ◽  
Male Mice ◽  
Sperm Development

AbstractKindlin-2 is known to play important roles in the development of mesoderm-derived tissues including myocardium, smooth muscle, cartilage and blood vessels. However, nothing is known for the role of Kindlin-2 in mesoderm-derived reproductive organs. Here, we report that loss of Kindlin-2 in Sertoli cells caused severe testis hypoplasia, abnormal germ cell development and complete infertility in male mice. Functionally, loss of Kindlin-2 inhibits proliferation, increases apoptosis, impairs phagocytosis in Sertoli cells and destroyed the integration of blood-testis barrier structure in testes. Mechanistically, Kindlin-2 interacts with LATS1 and YAP, the key components of Hippo pathway. Kindlin-2 impedes LATS1 interaction with YAP, and depletion of Kindlin-2 enhances LATS1 interaction with YAP, increases YAP phosphorylation and decreases its nuclear translocation. For clinical relevance, lower Kindlin-2 expression and decreased nucleus localization of YAP was found in SCOS patients. Collectively, we demonstrated that Kindlin-2 in Sertoli cells is essential for sperm development and male reproduction.

scholarly journals Importin α7 deficiency causes infertility in male mice by disrupting spermatogenesis

Development ◽  
2021 ◽  
Author(s):  
Na Liu ◽  
Fatimunnisa Qadri ◽  
Hauke Busch ◽  
Stefanie Huegel ◽  
Gabin Sihn ◽  
...  
Keyword(s):  
Sertoli Cells ◽  
Male Fertility ◽  
Target Genes ◽  
Cell Function ◽  
Expression Patterns ◽  
Male Mice ◽  
Loss Of Function ◽  
Altered Expression ◽  
Importin Α

Spermatogenesis is driven by an ordered series of events, which rely on trafficking of specific proteins between nucleus and cytoplasm. The importin α family of proteins mediates movement of specific cargo proteins when bound to importin β. Importin α genes have distinct expression patterns in mouse testis, implying they may have unique roles during mammalian spermatogenesis. Here we use a loss-of-function approach to specifically determine the role of importin α7 in spermatogenesis and male fertility. We show that ablation of importin α7 in male mice leads to infertility and has multiple cumulative effects on both germ cells and Sertoli cells. Importin α7-deficient mice exhibit an impaired Sertoli cell function, including loss of Sertoli cells and a compromised nuclear localization of the androgen receptor. Furthermore, our data demonstrate devastating defects in spermiogenesis including incomplete sperm maturation and massive loss of sperms that are accompanied by disturbed histone-protamine-exchange, differential localization of the transcriptional regulator Brwd1 and altered expression of Rfx2 target genes. Our work uncovers the essential role of importin α7 in spermatogenesis and hence in male fertility.

scholarly journals Importin α7 deficiency causes infertility in male mice by disrupting spermatogenesis

2020 ◽  
Author(s):  
Na Liu ◽  
Fatimunnisa Qadri ◽  
Hauke Busch ◽  
Stefanie Huegel ◽  
Gabin Sihn ◽  
...  
Keyword(s):  
Sertoli Cells ◽  
Male Fertility ◽  
Target Genes ◽  
Cell Function ◽  
Expression Patterns ◽  
Male Mice ◽  
Loss Of Function ◽  
Altered Expression ◽  
Importin Α

AbstractSpermatogenesis is driven by an ordered series of events, which rely on trafficking of specific proteins between nucleus and cytoplasm. The importin α family of proteins mediates movement of specific cargo proteins when bound to importin β. Importin α genes have distinct expression patterns in mouse testis, implying they may have unique roles during mammalian spermatogenesis. Here we use a loss-of-function approach to specifically determine the role of importin α7 in spermatogenesis and male fertility. We show that ablation of importin α7 in male mice leads to infertility and has multiple cumulative effects on both germ cells and Sertoli cells. Importin α7-deficient mice exhibit an impaired Sertoli cell function, including loss of Sertoli cells and a compromised nuclear transport of the androgen receptor. Furthermore, our data demonstrate devastating defects in spermiogenesis that are accompanied by disturbed histone-protamine-exchange, absence of the transcriptional regulator Brwd1 and altered expression of Rfx2 target genes, resulting in incomplete sperm maturation and massive loss of sperms. Our work uncovers the essential role of importin α7 in spermatogenesis and hence in male fertility.

scholarly journals Essential role for SUN5 in anchoring sperm head to the tail

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Yongliang Shang ◽  
Fuxi Zhu ◽  
Lina Wang ◽  
Ying-Chun Ouyang ◽  
Ming-Zhe Dong ◽  
...  
Keyword(s):  
Male Infertility ◽  
Nuclear Membrane ◽  
Essential Role ◽  
Sperm Head ◽  
The Sun ◽  
Male Mice ◽  
Nuclear Dynamics ◽  
Intracytoplasmic Injection

SUN (Sad1 and UNC84 domain containing)-domain proteins are reported to reside on the nuclear membrane playing distinct roles in nuclear dynamics. SUN5 is a new member of the SUN family, with little knowledge regarding its function. Here, we generated Sun5−/− mice and found that male mice were infertile. Most Sun5-null spermatozoa displayed a globozoospermia-like phenotype but they were actually acephalic spermatozoa. Additional studies revealed that SUN5 was located in the neck of the spermatozoa, anchoring sperm head to the tail, and without functional SUN5 the sperm head to tail coupling apparatus was detached from nucleus during spermatid elongation. Finally, we found that healthy heterozygous offspring could be obtained via intracytoplasmic injection of Sun5-mutated sperm heads for both male mice and patients. Our studies reveal the essential role of SUN5 in anchoring sperm head to the tail and provide a promising way to treat this kind of acephalic spermatozoa-associated male infertility.

scholarly journals CFAP61 is required for sperm flagellum formation and male fertility in human and mouse

2021 ◽  
Author(s):  
Siyu Liu ◽  
Jintao Zhang ◽  
Zine Eddine Kherraf ◽  
Shuya Sun ◽  
Xin Zhang ◽  
...  
Keyword(s):  
Male Fertility ◽  
Primary Ciliary Dyskinesia ◽  
Exon Skipping ◽  
Intraflagellar Transport ◽  
Transport Proteins ◽  
Radial Spoke ◽  
Sperm Flagellum ◽  
Cilia And Flagella ◽  
Ciliary Dyskinesia ◽  
Human And Mouse

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.

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