High frequency of <i>de novo DAZ</i> microdeletion in sperm nuclei of subfertile men: possible involvement of genome instability in idiopathic male infertility

Mozdarani, Hossein; Ghoraeian, Pegah; Mozdarani, Sohail; Fallahi, Parvin; Meybodi, Anahita Mohseni

doi:10.1080/14647273.2017.1322718

Cited by 9 publications

(4 citation statements)

References 54 publications

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“…However in the outmost side, the blood leukocytes AZFc deletion frequency in azoospermia patients is reported to be 10–15%. Although, recent report indicates that a high frequency of microdeletions in AZFc region especially DAZ gene might occur de novo during spermatogenesis when sperm nuclei are studied [8],[40]. Genome instability in azoospermia factor ( AZF ) region of Y chromosome especially in the DAZ genes was shown previously to occur in lymphocytes of men exposed to low dose and background level of ionizing radiation [31],[32] and in irradiated leukocytes in vitro [33].…”

Section: Discussionmentioning

confidence: 99%

High frequency of microdeletion in TTY2 gene family in peripheral blood leukocytes of non-obstructive azoospermia patients

et al. 2017

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About 10–15% of non-obstructive azoospermia (NOA) patients show AZFc microdeletion in their blood leukocytes. However, if AZF genes were involved in impaired spermatogenesis, a higher frequency of chromosomal microdeletions was expected. In this study the frequency of AZFc microdeletion was compared with TTY2 gene family, i.e., TTY2A2A and TTY2A12A in blood leukocytes of NOA patients and normal fertile control. In the present study 30 normal fertile individuals with mean age of 35.0 ± 6.0 and 30 NOA patients with mean age of 34.0 ± 7.0 were screened for microdeletion of TTY2L2A and TTY2L12A at Yq11 and Yp11 respectively and sequence-tagged site (STS) markers for AZFc gene using multiplex PCR technique. At the first step karyotyping was done for all subjects using standard G-banding technique to identify patients with normal karyotype as well as non-affected normal controls for molecular analysis. Results showed no AZFc microdeletion in normal and NAO patients whereas one TTY2L2A microdeletion in normal control (3.3%) and 4 in NOA (13.3%) was observed ( p < 0.05). However our data indicated that 6 of 30 NOA patients (20%) showed TTY2L12A microdeletion whereas there was no observed microdeletion in normal control ( p < 0.01). Results indicate that the studied genes might be involved in impaired spermatogenesis more effective than the routinely screened AZF genes in infertile men. Therefore, screening these genes along with AZF genes might be valuable for infertile patients. The reason why these genes are deleted from Y chromosome is not known but might be associated with genomic instability induced by environmental physico-chemical genotoxic agents.

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Section: Discussionmentioning

confidence: 99%

High frequency of microdeletion in TTY2 gene family in peripheral blood leukocytes of non-obstructive azoospermia patients

et al. 2017

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“…The authors concluded that this observation might be a possible explanation for induction of azoospermia and oligozoospermia after radiotherapy ( 48 ). Further studies by Mozdarani and Ghoraeian using a combined FISH and PRINS technique for detection of DAZ microdeletion in individual sperms showed considerably higher frequency of DAZ microdeletion in sperms of subfertile individuals whom their leukocytes were normal for DAZ gene ( 49 - 51 ).…”

Section: Yq Microdeletionmentioning

confidence: 96%

Basic and clinical genetic studies on male infertility in Iran during 2000-2016: A review

Moghbelinejad

Mozdarani

Ghoraeian

et al. 2018

IJRM

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The male factor contributes to 50% of infertility. The cause of male infertility is idiopathic and could be congenital or acquired. Among different factors which are involved in idiopathic male infertility, genetic factors are the most prevalent causes of the disease. Considering, the high prevalence of male infertility in Iran and the importance of genetic factors in the accession of it, in this article we reviewed the various studies which have been published during the last 17 yr on the genetic basis of male infertility in Iran. To do this, the PubMed and Scientific information database (SID) were regarded for the most relevant papers published in the last 17 yr referring to the genetics of male factor infertility using the keywords ‘‘genetics’’, “cytogenetic”, ‘‘male infertility”, and “Iranian population”. Literatures showed that among the Iranian infertile men Yq microdeletion and chromosomal aberrations are two main factors that intervene in the genetics of male infertility. Also, protamine deficiency (especially P2) is shown to have an influence on fertilization rate and pregnancy outcomes. The highest rate of sperm DNA damages has been found among the asthenospermia patients. In several papers, the relation between other important factors such as single gene mutations and polymorphisms with male infertility has also been reported. Recognition of the genetic factors that influence the fertility of Iranian men will shed light on the creation of guidelines for the diagnosis, consultation, and treatment of the patients."

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“…These data indicate that IAS with a “clean karyotype background” is one of the leading causes of male infertility 3 . Therefore, subtle genetic defects in the somatic cells of IAS males with a clean karyotype background, which may be missed by G-banding screening, need to be further investigated 4 .…”

Section: Introductionmentioning

confidence: 99%

Hypomethylation of the DAZ3 promoter in idiopathic asthenospermia: a screening tool for liquid biopsy

Zhang

et al. 2020

Sci Rep

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Given the role of the deleted in azoospermia gene in male infertility, whether the somatic deleted in azoospermia methylation status is associated with idiopathic asthenospermia should be determined. To investigate the methylation levels of the deleted in azoospermia promoter in peripheral white blood cells from idiopathic asthenospermia patients relative to those in normozoospermia controls, 61 ethylene diamine tetraacetic acid anticoagulant blood samples were drawn from all participants for DNA isolation. The deleted in azoospermia promoter methylation ratio was detected by MassARRAY-based methylation quantification and confirmed by quantitative methylation-specific polymerase chain reaction. A MassARRAY-based methylation analysis showed that the deleted in azoospermia 3 promoter (0 to − 2 kbp) was significantly hypomethylated in peripheral white blood cells from idiopathic asthenospermia males, specifically one CpG site (− 246 to − 247). Quantitative methylation-specific polymerase chain reaction data further confirmed that the methylation level of the deleted in azoospermia 3 promoter region in idiopathic asthenospermia patients was significantly lower than that in normozoospermia males. The area under the receiver operating characteristic curve determined by quantitative methylation-specific polymerase chain reaction was 0.737 (95% confidence interval: 0.552 to 0.924), with a sensitivity of 53.9% and a specificity of 88.2% at a cut-off level of 74.7%. Therefore, our results suggested that methylation ratio detection of the deleted in azoospermia 3 promoter region by real-time polymerase chain reaction assay is a promising and feasible tool for liquid biopsy in the clinical laboratories. The methylation status of other reported infertility-related genes should also be investigated in peripheral white blood cells.

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High frequency of de novo DAZ microdeletion in sperm nuclei of subfertile men: possible involvement of genome instability in idiopathic male infertility

Cited by 9 publications

References 54 publications

High frequency of microdeletion in TTY2 gene family in peripheral blood leukocytes of non-obstructive azoospermia patients

High frequency of microdeletion in TTY2 gene family in peripheral blood leukocytes of non-obstructive azoospermia patients

Basic and clinical genetic studies on male infertility in Iran during 2000-2016: A review

Hypomethylation of the DAZ3 promoter in idiopathic asthenospermia: a screening tool for liquid biopsy

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