Mutation analysis in patients with total sperm immotility

Pereira, Rute; Oliveira, Jorge; Ferráz, Luís; Barros, Alberto; Santos, Rosário; Sousa, Mário

doi:10.1007/s10815-015-0474-6

Cited by 37 publications

(32 citation statements)

References 56 publications

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“…However, there are no consensus if DFS is a genetic disorder. Indeed, no association between DFS and defects in genes that code for AKAP3 and AKAP4 proteins were found 110111112…”

Section: Main Factors Affecting Sperm Motilitymentioning

confidence: 99%

Major regulatory mechanisms involved in sperm motility

Pereira¹,

Sá²,

Barros³

et al. 2017

Asian J Androl

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229

171

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The genetic bases and molecular mechanisms involved in the assembly and function of the flagellum components as well as in the regulation of the flagellar movement are not fully understood, especially in humans. There are several causes for sperm immotility, of which some can be avoided and corrected, whereas other are related to genetic defects and deserve full investigation to give a diagnosis to patients. This review was performed after an extensive literature search on the online databases PubMed, ScienceDirect, and Web of Science. Here, we review the involvement of regulatory pathways responsible for sperm motility, indicating possible causes for sperm immotility. These included the calcium pathway, the cAMP-dependent protein kinase pathway, the importance of kinases and phosphatases, the function of reactive oxygen species, and how the regulation of cell volume and osmolarity are also fundamental components. We then discuss main gene defects associated with specific morphological abnormalities. Finally, we slightly discuss some preventive and treatments approaches to avoid development of conditions that are associated with unspecified sperm immotility. We believe that in the near future, with the development of more powerful techniques, the genetic causes of sperm immotility and the regulatory mechanisms of sperm motility will be better understand, thus enabling to perform a full diagnosis and uncover new therapies.

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“…However, there are no consensus if DFS is a genetic disorder. Indeed, no association between DFS and defects in genes that code for AKAP3 and AKAP4 proteins were found 110111112…”

Section: Main Factors Affecting Sperm Motilitymentioning

confidence: 99%

Major regulatory mechanisms involved in sperm motility

Pereira¹,

Sá²,

Barros³

et al. 2017

Asian J Androl

Self Cite

229

171

View full text Add to dashboard Cite

show abstract

“…The Akap4defficient mice resemble the asthenozoospermic phenotype (Fang et al 2019) observed in men. However, apart from these two case reports, AKAP4 mutations were not found in other cohorts of DFS patients, indicating currently limited evidence for this gene defect (Turner et al 2001a, b;Yang et al 2015b;Pereira et al 2015).…”

Section: Akap4mentioning

confidence: 83%

The X chromosome and male infertility

et al. 2019

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The X chromosome is a key player in germ cell development, as has been highlighted for males in previous studies revealing that the mammalian X chromosome is enriched in genes expressed in early spermatogenesis. In this review, we focus on the X chromosome's unique biology as associated with human male infertility. Male infertility is most commonly caused by spermatogenic defects to which X chromosome dosage is closely linked; for example, any supernumerary X chromosome as in Klinefelter syndrome will lead to male infertility. Furthermore, because males normally only have a single X chromosome and because X-linked genetic anomalies are generally only present in a single copy in males, any loss-of-function mutations in single-copy X-chromosomal genes cannot be compensated by a normal allele. These features make X-linked genes particularly attractive for studying male spermatogenic failure. However, to date, only very few genetic causes have been identified as being definitively responsible for male infertility in humans. Although genetic studies of germ cell-enriched X-chromosomal genes in mice suggest a role of certain human orthologs in infertile men, these genes in mice and humans have striking evolutionary differences. Furthermore, the complexity and highly repetitive structure of the X chromosome hinder the mutational analysis of X-linked genes in humans. Therefore, we conclude that additional methodological approaches are urgently warranted to advance our understanding of the genetics of X-linked male infertility.Matthias Vockel and Antoni Riera-Escamilla are co-first authors.Frank Tüttelmann and Csilla Krausz are co-last authors.

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“…In the report of Moretti et al ., a weak labelling for AKAP4 was demonstrated in the group of patients with severely reduced sperm motility and disorganised FS; however, none of these cases was characterised by the typical for DFS ultrastructural features of the sperm flagellum (Moretti et al ., ). The subsequent report did not add further evidence towards the hypothesis that Akap 3/4 are the genetic causes of the DFS phenotype (Pereira et al ., ). Thus, the role of AKAP3/4 genetic mutation in the development of DFS was described only in one DFS case (Baccetti et al ., ).…”

Section: Discussionmentioning

confidence: 97%

“…demonstrated a partial deletion in AKAP4 and AKAP3 genes and the absence of the protein AKAP4 in one of five patients with DFS (Baccetti et al ., ). At the same time, other researches revealed no differences in the content of the proteins AKAP4 or AKAP3 in DFS spermatozoa compared to normal spermatozoa (Turner et al ., ; Moretti et al ., ; Pereira et al ., ). Recently, four homozygous mutations in the DNAH1 gene encoding for axonemal inner arm dynein heavy chains were identified in seven patients with MMAF (Ben Khelifa et al ., ).…”

Section: Introductionmentioning

confidence: 97%

Detection of a mutation in the intron of Sperm-specific glyceraldehyde-3-phosphate dehydrogenase gene in patients with fibrous sheath dysplasia of the sperm flagellum

et al. 2016

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The fibrous sheath is a unique cytoskeletal structure surrounding the axoneme and outer dense fibres of the sperm flagellum. Dysplasia of the fibrous sheath (DFS) is a defect of spermatozoa observed in severe asthenozoospermic patients and characterised by morphologically abnormal flagella with distorted fibrous sheaths. Sperm-specific glyceraldehyde-3-phosphate dehydrogenase (GAPDS) is a glycolytic enzyme that is tightly associated with the fibrous sheath of the sperm flagellum. The enzymatic activity of GAPDS was investigated in sperm samples of seven patients with DFS and compared to that of normal spermatozoa (n = 10). The difference in GAPDS activity in DFS and normal spermatozoa was statistically significant (0.19 ± 0.11 and 0.75 ± 0.11 μmol NADH per min per mg protein respectively). Immunochemical staining revealed irregular distribution of GAPDS in the flagellum of DFS spermatozoa. Other five samples with typical alterations in the fibrous sheath were assayed for mutations within human GAPDS gene. In all five cases, a replacement of guanine by adenine was revealed in the intron region between the sixth and the seventh exons of GAPDS. It is assumed that the deficiency in GAPDS observed in most DFS sperm samples is ascribable to a disorder in the regulation of GAPDS expression caused by the mutation in the intron region of GAPDS gene.

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Mutation analysis in patients with total sperm immotility

Cited by 37 publications

References 56 publications

Major regulatory mechanisms involved in sperm motility

Major regulatory mechanisms involved in sperm motility

The X chromosome and male infertility

Detection of a mutation in the intron of Sperm-specific glyceraldehyde-3-phosphate dehydrogenase gene in patients with fibrous sheath dysplasia of the sperm flagellum

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