A comprehensive gene mutation screen in men with asthenozoospermia

Visser, Liesbeth; Westerveld, G.H.; Xie, Fang; Daalen, Saskia K.M. van; Veen, Fulco van der; Lombardi, Maria; Repping, Sjoerd

doi:10.1016/j.fertnstert.2010.11.067

Cited by 31 publications

(24 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The typical phenotype of large headed sperm cells is especially detected in North African men, where the carrier frequency of the mutation is estimated to be 1/50. 29,30 Visser et al 31 analysed 30 patients with isolated asthenozoospermia for the presence of mutations in nine genes that were selected on the basis of the phenotype observed in knockout mouse models. They identified four CATSPER genes, which form the ion channel essential for the calcium influx during sperm capacitation.…”

Section: Single-gene Defectsmentioning

confidence: 99%

“…The genes GAPDHS, PLA2G6 and ADCY10 code for enzymes specifically expressed in sperm, and SLC9A10 is a sodium hydrogen exchanger. 31 A total of 10 potential mutations were detected in seven of these genes (ADCY10, AKAP4, CATSPER1, CATSPER2, CATSPER3, CATSPER4 and PLA2G6), yet all of the changes were heterozygous alterations. However, three patients had multiple changes in the investigated genes.…”

Section: Single-gene Defectsmentioning

confidence: 99%

See 1 more Smart Citation

Genetic causes of spermatogenic failure

Massart¹,

Lissens²,

Tournaye³

et al. 2011

Asian J Androl

167

124

View full text Add to dashboard Cite

Approximately 10%-15% of couples are infertile, and a male factor is involved in almost half of these cases. This observation is due in part to defects in spermatogenesis, and the underlying causes, including genetic abnormalities, remain largely unknown. Until recently, the only genetic tests used in the diagnosis of male infertility were aimed at detecting the presence of microdeletions of the long arm of the Y chromosome and/or chromosomal abnormalities. Various other single-gene or polygenic defects have been proposed to be involved in male fertility. However, their causative effects often remain unproven. The recent evolution in the development of whole-genome-based techniques and the large-scale analysis of mouse models might help in this process. Through knockout mouse models, at least 388 genes have been shown to be associated with spermatogenesis in mice. However, problems often arise when translating this information from mice to humans.

show abstract

Section: Single-gene Defectsmentioning

confidence: 99%

Section: Single-gene Defectsmentioning

confidence: 99%

Genetic causes of spermatogenic failure

Massart¹,

Lissens²,

Tournaye³

et al. 2011

Asian J Androl

167

124

View full text Add to dashboard Cite

show abstract

“…There are several factors influencing sperm motility, including respective gene expression, anomalies in flagellum (i.e. mitochondria) and environmental factors (Terai et al 2010, Moretti et al 2011, Pelliccione et al 2011, Visser et al 2011, Ferramosca et al 2012. Thus, it cannot be ruled out that some of these genes were interrupted or mutated and their expression change constituted an indirect factor that decreased the motility of sperm cells.…”

Section: Discussionmentioning

confidence: 99%

Sperm FISH and chromatin integrity in spermatozoa from a t(6;10;11) carrier

Olszewska

Huleyuk²,

Frączek³

et al. 2014

Reproduction

View full text Add to dashboard Cite

Complex chromosome rearrangements (CCRs) are structurally balanced or unbalanced aberrations involving more than two breakpoints on two or more chromosomes. CCRs can be a potential reason for genomic imbalance in gametes, which leads to a drastic reduction in fertility. In this study, the meiotic segregation pattern, aneuploidy of seven chromosomes uninvolved in the CCR and chromatin integrity were analysed in the ejaculated spermatozoa of a 46,XY,t(6;10;11)(q25.1;q24.3;q23.1)mat carrier with asthenozoospermia and a lack of conception. The frequency of genetically unbalanced spermatozoa was 78.8% with a prevalence of 4:2 segregants of 38.2%, while the prevalence of the adjacent 3:3 mode was 35.3%. Analysis of the aneuploidy of chromosomes 13, 15, 18, 21, 22, X and Y revealed an approximately fivefold increased level in comparison with that of the control group, indicating the presence of an interchromosomal effect. Sperm chromatin integrity status was evaluated using chromomycin A3 and aniline blue staining (deprotamination), acridine orange test and TUNEL assay (sperm DNA fragmentation). No differences were found when comparisons were made with a control group. We suggest that the accumulation of genetically unbalanced spermatozoa, significantly increased sperm aneuploidy level and decreased sperm motility (20%, progressive) were not responsible for the observed lack of reproductive success in the analysed infertile t(6;10;11) carrier. Interestingly, in the case described herein, a high level of sperm chromosomal imbalance appears not to be linked to sperm chromatin integrity status.

show abstract

“…Intragenic deletions of the AKAP3 and AKAP4 genes were first described in a patient with total sperm immotility due to dysplasia of the fibrous sheath (DFS) (Baccetti et al 2005). In 2011, an additional patient with DFS was reported carrying a hemizygous missense variant in AKAP4 (Visser et al 2011). The Akap4defficient mice resemble the asthenozoospermic phenotype (Fang et al 2019) observed in men.…”

Section: Akap4mentioning

confidence: 99%

The X chromosome and male infertility

et al. 2019

View full text Add to dashboard Cite

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.

show abstract

A comprehensive gene mutation screen in men with asthenozoospermia

Cited by 31 publications

References 31 publications

Genetic causes of spermatogenic failure

Genetic causes of spermatogenic failure

Sperm FISH and chromatin integrity in spermatozoa from a t(6;10;11) carrier

The X chromosome and male infertility

Contact Info

Product

Resources

About