Nexin-Dynein regulatory complex component DRC7 but not FBXL13 is required for sperm flagellum formation and male fertility in mice

Morohoshi, Akane; Miyata, Haruhiko; Shimada, Keisuke; Nozawa, Kaori; Matsumura, Takafumi; Yanase, Ryuji; Shiba, Kogiku; Inaba, Kazuo; Ikawa, Masahito

doi:10.1371/journal.pgen.1008585

Cited by 39 publications

(45 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…dynein regulatory complex [6,[32][33][34] and of Kinesin Family Member 9, KIF9, that is associated with axoneme and flagellar movement [35][36][37][38]. The analysis did not detect major differences in intensity of RSPH6A, DRC3 and KIF9 protein bands in control Cfap97d1 wt/em1 and Cfap97-d1 em1/em1 sperm lysates (S6D Fig).…”

Section: Plos Geneticsmentioning

confidence: 91%

Cfap97d1 is important for flagellar axoneme maintenance and male mouse fertility

et al. 2020

Self Cite

View full text Add to dashboard Cite

The flagellum is essential for sperm motility and fertilization in vivo. The axoneme is the main component of the flagella, extending through its entire length. An axoneme is comprised of two central microtubules surrounded by nine doublets, the nexin-dynein regulatory complex, radial spokes, and dynein arms. Failure to properly assemble components of the axoneme in a sperm flagellum, leads to fertility alterations. To understand this process in detail, we have defined the function of an uncharacterized gene, Cfap97 domain containing 1 (Cfap97d1). This gene is evolutionarily conserved in mammals and multiple other species, including Chlamydomonas. We have used two independently generated Cfap97d1 knockout mouse models to study the gene function in vivo. Cfap97d1 is exclusively expressed in testes starting from post-natal day 20 and continuing throughout adulthood. Deletion of the Cfap97d1 gene in both mouse models leads to sperm motility defects (asthenozoospermia) and male subfertility. In vitro fertilization (IVF) of cumulus-intact oocytes with Cfap97d1 deficient sperm yielded few embryos whereas IVF with zona pellucida-free oocytes resulted in embryo numbers comparable to that of the control. Knockout spermatozoa showed abnormal motility characterized by frequent stalling in the anti-hook position. Uniquely, Cfap97d1 loss caused a phenotype associated with axonemal doublet heterogeneity linked with frequent loss of the fourth doublet in the sperm stored in the epididymis. This study demonstrates that Cfap97d1 is required for sperm flagellum ultra-structure maintenance, thereby playing a critical role in sperm function and male fertility in mice.

show abstract

Section: Plos Geneticsmentioning

confidence: 91%

Cfap97d1 is important for flagellar axoneme maintenance and male mouse fertility

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…RNF216 is essential for spermatogenesis and male fertility 304 . The deletion of Drc7 leads to aberrant tail formation in mouse spermatozoa that phenocopies patients with multiple morphological abnormalities of the sperm flagella (MMAF) 305 . These two proteins were reduced in COVID-19 patients (SI Figure 15), suggesting the impairment of spermatogenesis and sperm motility caused by SARS-CoV-2 infection.…”

Section: Testismentioning

confidence: 99%

Multi-organ Proteomic Landscape of COVID-19 Autopsies

Nie¹,

Qian²,

Sun³

et al. 2020

Preprint

149

View full text Add to dashboard Cite

The molecular pathology of multi-organ injuries in COVID-19 patients remains unclear, preventing effective therapeutics development. Here, we report an in-depth multi-organ proteomic landscape of COVID-19 patient autopsy samples. By integrative analysis of proteomes of seven organs, namely lung, spleen, liver, heart, kidney, thyroid and testis, we characterized 11,394 proteins, in which 5336 were perturbed in COVID-19 patients compared to controls. Our data showed that CTSL, rather than ACE2, was significantly upregulated in the lung from COVID-19 patients. Dysregulation of protein translation, glucose metabolism, fatty acid metabolism was detected in multiple organs. Our data suggested upon SARS-CoV-2 infection, hyperinflammation might be triggered which in turn induces damage of gas exchange barrier in the lung, leading to hypoxia, angiogenesis, coagulation and fibrosis in the lung, kidney, spleen, liver, heart and thyroid. Evidence for testicular injuries included reduced Leydig cells, suppressed cholesterol biosynthesis and sperm mobility. In summary, this study depicts the multi-organ proteomic landscape of COVID-19 autopsies, and uncovered dysregulated proteins and biological processes, offering novel therapeutic clues.

show abstract

“…Periodic acid–Schiff (PAS) staining of sections were performed as previously described [ 30 ]. Testes or epididymis were fixed in Bouin solution (Polysciences, Inc., Warrington, PA) and were processed for paraffin embedding.…”

Section: Methodsmentioning

confidence: 99%

“…The primers used are listed in Supplementary Table S1 . FLAG-tagged Drc7 vector and PA-tagged Drc3 vector were described previously [ 30 ].…”

Section: Methodsmentioning

confidence: 99%

CIB4 is essential for the haploid phase of spermatogenesis in mice†

Miyata

Kaneda

et al. 2020

Biology of Reproduction

Self Cite

View full text Add to dashboard Cite

Spermatogenesis is a complex developmental process that involves the proliferation of diploid cells, meiotic division, and haploid differentiation. Many genes are shown to be essential for male fertility using knockout (KO) mice; however, there still remain genes to be analyzed to elucidate their molecular mechanism and their roles in spermatogenesis. Calcium- and integrin-binding protein 1 (CIB1) is a ubiquitously expressed protein that possesses three paralogs: CIB2, CIB3, and CIB4. It is reported that Cib1 KO male mice are sterile due to impaired haploid differentiation. In this study, we discovered that Cib4 is expressed strongly in mouse and human testis and begins expression during the haploid phase of spermatogenesis in mice. To analyze the function of CIB4 in vivo, we generated Cib4 KO mice using the CRISPR/Cas9 system. Cib4 KO male mice are sterile due to impaired haploid differentiation, phenocopying Cib1 KO male mice. Spermatogenic cells isolated from seminiferous tubules demonstrate an essential function of CIB4 in the formation of the apical region of the sperm head. Further analysis of CIB4 function may shed light on the etiology of male infertility caused by spermatogenesis defects, and CIB4 could be a target for male contraceptives because of its dominant expression in the testis. Summary sentence Cib4 mutant mice exhibit male infertility due to impaired spermiogenesis.

show abstract

Nexin-Dynein regulatory complex component DRC7 but not FBXL13 is required for sperm flagellum formation and male fertility in mice

Cited by 39 publications

References 58 publications

Cfap97d1 is important for flagellar axoneme maintenance and male mouse fertility

Cfap97d1 is important for flagellar axoneme maintenance and male mouse fertility

Multi-organ Proteomic Landscape of COVID-19 Autopsies

CIB4 is essential for the haploid phase of spermatogenesis in mice†

Contact Info

Product

Resources

About