Cdc14a has a role in spermatogenesis, sperm maturation and male fertility

Wen, Zongzhuang; Zhu, Haixia; Zhang, Aizhen; Lin, Jing; Zhang, Guangkai; Liu, Dongyue; Yu, Xiao; Ye, Chao; Sun, Daqing; Wu, Bin; Zhang, Jian; Gao, Jiangang

doi:10.1016/j.yexcr.2020.112178

Cited by 10 publications

(7 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many DEGs in elongated spermatid have been reported to be closely related to spermiogenesis. For example, Smcp , Sord , Atp1a4 , Cdc14a and Pgk2 are all important for sperm motility 34 , 35 , 36 , 37 , 38 ; Akap4 and Spem1 deletion results in sperm deformity 39 , 40 ; and Pmis2 null sperm fails to bind to the zona pellucida 41 (Figure 3E ). Together, the transcriptome of Ythdf2 ‐vKO germ cells changed mainly thereafter pachytene stage, and the DEGs were coincident with the sperm malformation, impaired motility and loss of fertilization capacity in Ythdf2 ‐vKO mice.…”

Section: Resultsmentioning

confidence: 99%

m⁶A reader protein YTHDF2 regulates spermatogenesis by timely clearance of phase‐specific transcripts

Sun

Guo

et al. 2021

Cell Proliferation

View full text Add to dashboard Cite

Objectives Accumulating evidences show that the regulatory network of m 6 A modification is essential for mammalian spermatogenesis. However, as an m 6 A reader, the roles of YTHDF2 remain enigmatic due to the lack of a proper model. Here, we employed the germ cell conditional knockout mouse model and explored the function of YTHDF2 in spermatogenesis. Materials and methods Ythdf2 germ cell conditional knockout mice were obtained by crossing Ythdf2 ‐floxed mice with Vasa ‐ Cre and Stra8 ‐ Cre mice. Haematoxylin and eosin (HE) staining, immunofluorescent staining and Western blotting were used for phenotyping. CASA, IVF and ICSI were applied for sperm function analysis. RNA‐seq, YTHDF2‐RIP‐seq and quantitative real‐time PCR were used to explore transcriptome changes and molecular mechanism analysis. Results Our results showed that YTHDF2 was highly expressed in spermatogenic cells. The germ cell conditional knockout males were sterile, and their sperm displayed malformation, impaired motility, and lost fertilization ability. During differentiated spermatogonia transiting to pachytene spermatocyte, most m 6 A‐modified YTHDF2 targets that were degraded in control germ cells persisted in pachytene spermatocytes of Ythdf2 ‐vKO mice. These delayed mRNAs were mainly enriched in pathways related to the regulation of transcription, and disturbed the transcriptome of round spermatid and elongated spermatid subsequently. Conclusion Our data demonstrate that YTHDF2 facilitates the timely turnover of phase‐specific transcripts to ensure the proper progression of spermatogenesis, which highlights a critical role of YTHDF2 in spermatogenesis.

show abstract

Section: Resultsmentioning

confidence: 99%

m⁶A reader protein YTHDF2 regulates spermatogenesis by timely clearance of phase‐specific transcripts

Sun

Guo

et al. 2021

Cell Proliferation

View full text Add to dashboard Cite

show abstract

“…In zebrafish, CDC14A and CDC14B are necessary for proper cilia elongation and/or maintenance, providing the first evidence of functional redundancy between these phosphatases (Clement et al , 2012). The analysis of mouse models with single mutations has also suggested some specific but molecular undefined functions in meiosis or aging (Imtiaz et al , 2018; Wen et al , 2020). Mutations of CDC14A in patients with autosomal‐recessive severe to profound deafness suggest additional roles in hearing (Delmaghani et al , 2016; Imtiaz et al , 2018).…”

Section: Discussionmentioning

confidence: 99%

Mammalian CDC14 phosphatases control exit from stemness in pluripotent cells

et al. 2022

View full text Add to dashboard Cite

Maintenance of stemness is tightly linked to cell cycle regulation through protein phosphorylation by cyclin‐dependent kinases (CDKs). However, how this process is reversed during differentiation is unknown. We report here that exit from stemness and differentiation of pluripotent cells along the neural lineage are controlled by CDC14, a CDK‐counteracting phosphatase whose function in mammals remains obscure. Lack of the two CDC14 family members, CDC14A and CDC14B, results in deficient development of the neural system in the mouse and impairs neural differentiation from embryonic stem cells (ESCs). Mechanistically, CDC14 directly dephosphorylates specific proline‐directed Ser/Thr residues of undifferentiated embryonic transcription Factor 1 (UTF1) during the exit from stemness, triggering its proteasome‐dependent degradation. Multiomic single‐cell analysis of transcription and chromatin accessibility in differentiating ESCs suggests that increased UTF1 levels in the absence of CDC14 prevent the proper firing of bivalent promoters required for differentiation. CDC14 phosphatases are dispensable for mitotic exit, suggesting that CDC14 phosphatases have evolved to control stemness rather than cell cycle exit and establish the CDK‐CDC14 axis as a critical molecular switch for linking cell cycle regulation and self‐renewal.

show abstract

“…Sperms were isolated from the cauda epididymis as previously described 21 . The cauda epididymis was dissected from an adult mouse and cut into pieces in a 500 μl M2 medium (Sigma‐Aldrich, Missouri, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Sperms were isolated from the cauda epididymis as previously described. 21 The cauda epididymis was dissected from an adult mouse and cut into pieces in a 500 μl M2 medium (Sigma-Aldrich, Missouri, USA). The sperms were exuded from incisions of the cauda epididymis for 30 min at 37°C under 5% CO 2 .…”

Section: Computer-assisted Sperm Analysismentioning

confidence: 99%

Hadhdeficiency induced oligoasthenoteratozoospermia through theTNF‐α/Bcl‐2 pathway in male mice

et al. 2022

Self Cite

View full text Add to dashboard Cite

The process of spermatogenesis is a complex and delicate process that is still not fully understood. In this study, we examined the role of fatty acid oxidase 3-hydroxy acyl CoA dehydrogenase (HADH) in maintaining normal spermatogenesis in mice. In male mice, ablation of the Hadh gene using CRISPR/Cas9 technology arrested spermatocyte meiosis, increased multinucleated giant germ cells and vacuoles in seminiferous tubules, and accompanied with acrosomal dysplasia. Hadh −/− male mice showed the typical features of oligoasthenoteratozoospermia (OAT), including decreased sperm concentration and motility and increased sperm abnormalities. Next, we explored the molecular events in the testes of the mutant mice. We found fatty acids accumulated in the testis of Hadh −/− mice. And also, inflammatory factors TNF-α, IL-1β, and IL-6 were significantly increased, apoptosis-related protein Bcl-2 was decreased, and Bax and cleaved-Caspase3 were increased in Hadh −/− male mice testis. After using etanercept, a specific inhibitor of TNF-α, testis injury caused by Hadh knockout was significantly alleviated, the sperm quality and motility were improved, and germ cell apoptosis was reduced. So our study demonstrated that Hadh deletion caused an increase in fatty acids. The accumulated fatty acids further induced testicular inflammation and germ cell apoptosis through the TNF-α/Bcl-2 signaling pathway, finally resulting in OAT in the Hadh −/− mice. Inhibiting TNF-α may be used as a new treatment approach for testicular inflammation and OAT.

show abstract

Cdc14a has a role in spermatogenesis, sperm maturation and male fertility

Cited by 10 publications

References 52 publications

m⁶A reader protein YTHDF2 regulates spermatogenesis by timely clearance of phase‐specific transcripts

m⁶A reader protein YTHDF2 regulates spermatogenesis by timely clearance of phase‐specific transcripts

Mammalian CDC14 phosphatases control exit from stemness in pluripotent cells

Hadhdeficiency induced oligoasthenoteratozoospermia through theTNF‐α/Bcl‐2 pathway in male mice

Contact Info

Product

Resources

About

Cdc14a has a role in spermatogenesis, sperm maturation and male fertility

Cited by 10 publications

References 52 publications

m6A reader protein YTHDF2 regulates spermatogenesis by timely clearance of phase‐specific transcripts

m6A reader protein YTHDF2 regulates spermatogenesis by timely clearance of phase‐specific transcripts

Mammalian CDC14 phosphatases control exit from stemness in pluripotent cells

Hadhdeficiency induced oligoasthenoteratozoospermia through theTNF‐α/Bcl‐2 pathway in male mice

Contact Info

Product

Resources

About

m⁶A reader protein YTHDF2 regulates spermatogenesis by timely clearance of phase‐specific transcripts

m⁶A reader protein YTHDF2 regulates spermatogenesis by timely clearance of phase‐specific transcripts