Loss of CEP70 function affects acrosome biogenesis and flagella formation during spermiogenesis

Liu, Qiang; Guo, Qingping; Guo, Wei; Song, Shuangshuang; Wang, Nan; Chen, Xi; Sun, Andi; Yan, Liying; Qiao, Jie

doi:10.1038/s41419-021-03755-z

Cited by 14 publications

(13 citation statements)

References 66 publications

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“…Previous data showed that CEP70 is involved in cilia formation and determines the length of the axoneme in zebrafish embryos ( 21 ). A recent study suggested that Cep70 −/− in mice caused male infertility, which resulted in abnormal acrosome structure and abnormal flagella ( 14 ). Furthermore, mice lacking CEP70 also exhibited disturbed spermiogenesis and increased germ-cell apoptosis, which led to a decrease in sperm count ( 14 ).…”

Section: Discussionmentioning

confidence: 99%

“…CEP70 was first found in proteomics studies of the centrosome and was suggested to express in the sperm tail ( 12 , 13 ). However, only one study has suggested that loss of CEP70 function is involved in male infertility ( 14 ). In that study, the authors found that CEP70 deficiency leads to male infertility in mice, which is associated with abnormalities in sperm flagellum, head and acrosome, and heterozygous mutations of CEP70 in four azoospermia patients were detected ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

“…However, only one study has suggested that loss of CEP70 function is involved in male infertility ( 14 ). In that study, the authors found that CEP70 deficiency leads to male infertility in mice, which is associated with abnormalities in sperm flagellum, head and acrosome, and heterozygous mutations of CEP70 in four azoospermia patients were detected ( 14 ). Therefore, the role of CEP70 in human fertility needs to be further explored.…”

Section: Introductionmentioning

confidence: 99%

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Identification of biallelic variations of CEP70 in patients with male infertility

Ruan

Yang²,

Jiang³

et al. 2023

Front. Endocrinol.

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IntroductionMale infertility is a severe health issue caused by complex and multifactorial pathological conditions. Genetic factors are a major cause of male infertility. CEP70, a centrosomal protein, has been reported to play an important role in male reproduction in mice. However, the role of CEP70 in human male infertility is limited.MethodsWhole exome sequencing and Sanger sequencing were used to identify the genetic cause of the infertile patients. Papanicolaou staining, scanning electron microscopy and transmission electron microscopy were further conducted to explore morphological and ultrastructural defects in spermatozoa from the patient. Immunofluorescence staining was used to detect the pathogenicity of the identified variants and the particular expression of CEP70 in testis.ResultsIn this study, we identified biallelic mutations of CEP70 in two unrelated infertile male individuals with oligoasthenoteratozoospermia that followed a recessive inheritance pattern. Papanicolaou staining, scanning electron microscopy and transmission electron microscopy showed that morphological and ultrastructural defects in the acrosome and flagellum of sperm from the patient in a pattern strikingly similar to that in Cep70−/− male mice. The results of immunofluorescence staining suggested that CEP70 was normally expressed in the acrosome and flagellum of control sperm but was hardly detected in the sperm of patient carrying CEP70 variation. We also explored the particular expression pattern of CEP70 during spermatogenesis in humans and mice.ConclusionsBiallelic mutations of CEP70 might be a novel genetic cause of human male infertility, which could potentially serve as a basis for genetic counseling and diagnosis of male infertility.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of biallelic variations of CEP70 in patients with male infertility

Ruan

Yang²,

Jiang³

et al. 2023

Front. Endocrinol.

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“…Besides, acrosome development has a key role in this process. So far, more than 4000 genes have been reported to be involved in human spermatogenesis 4 . However, it is assumed that many genetic factors, which are yet to be discovered, can also affect spermatogenesis.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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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.

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“…Approximately 10-15% of couples (50-80 million people) within the reproductive age are suffering from the condition of infertility, according to the recently revealed data by the World Health Organization (WHO). 1 Males are about 50% of the reported infertility cases. 2 Azoospermia can be described as the absence of sperms in two separately collected semen samples following centrifugation (1000×g for about 15 min).…”

Section: Introductionmentioning

confidence: 99%

Follicle-stimulating hormone (FSH) receptor gene polymorphisms in Iraqi patients with non-obstructive azoospermia

Ali

Abdul‐Rasheed

Al-Kawaz

2021

Baghdad J. Biochem. Appl. Biol. Sci.

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Background: Follicle-stimulating hormone (FSH) is a pivotal hormone for male fertility, and its action on gonads is exerted by FSH receptors (FSHRs). Objectives: To examine whether the presence of FSHR gene single nucleotide polymorphisms (SNPs), G919A and A2039G, involved in non-obstructive azoospermia (NOA) in Iraqi infertile men. Methods: Two common SNPs, A919G and A2039G, in the FSHR gene were analyzed in 104 subjects (70 infertile patients with NOO: 33 NOA patients were not receiving treatment and 37 were on infertility treatment, and 34 normozoospermic fertile men as controls). Results: The results revealed that the homozygous wild genotype (AA) of rs6165 FSHR gene SNP was more abundant than (AG) and (GG) genotypes in both groups of infertile NOA patients with a frequency of 49% in those who untreated, 81% in patients undergoing treatment and in the control group 41%. Whereas, the highest percentage of heterozygous genotype (AG) in the fertile control group was 41% when compared to NOApatients with a genotype frequency of 24% (for those who untreated) and 11% (for patients on treatment), respectively; with (A) allele frequency of 86% and the observed frequency of (G) allele was only 14% in the patients’ group as compared to that of controls that were (65 %) and (35 %), respectively. The rs6166 genotyping revealed that the homozygous wild genotype (GG) of FSHR gene was more abundant than (AG) and (AA) genotypes in NOA patients receiving infertility treatment with a frequency of (68%), in NOA patients who didn’t receive treatment 49%, while the lowest frequency was detected in the healthy fertile control group (47%). Conclusions: These results support the evidence that rs6165 and rs6166, FSHR SNPs, might be involved in the pathogenesis and protection against NOA, respectively.

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Loss of CEP70 function affects acrosome biogenesis and flagella formation during spermiogenesis

Cited by 14 publications

References 66 publications

Identification of biallelic variations of CEP70 in patients with male infertility

Identification of biallelic variations of CEP70 in patients with male infertility

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

Follicle-stimulating hormone (FSH) receptor gene polymorphisms in Iraqi patients with non-obstructive azoospermia

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