Associations of single nucleotide polymorphisms in the Pygo2 coding sequence with idiopathic oligospermia and azoospermia

Sq, Ge; Grifin, J; Lh, Liu; Ki, Aston; Lee, Simon; Jenkins, Timothy G.; Br, Emery; Dt, Carrell

doi:10.4238/2015.august.7.14

Cited by 6 publications

(8 citation statements)

References 34 publications

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“…Our findings add to the growing literature on genetic reasons for infertility (Chen et al, 2015;El Inati et al, 2012;Ferlin and Foresta, 2014;Ge et al, 2015;Plaseski et al, 2012;Sato et al, 2015). It is well known that both autosomal and sex chromosome genes are involved in the complex regulation of spermatogenesis (Guo et al, 2012;Singh and Jaiswal, 2011).…”

Section: Discussionsupporting

confidence: 77%

“…Genetic make-up may also influence the response and outcome of assisted reproductive treatment (Venkatesh et al, 2014). It is estimated that 10-15% of spermatogenic impairment is explained by genetic defects (Ferlin and Foresta, 2014), and furthermore, association studies propose gene polymorphisms to affect spermatogenesis, which in turn may lead to oligozoospermia-or azoospermia-induced male infertility (Chen et al, 2015;Ge et al, 2015;Plaseski et al, 2012;Sato et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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The effect of a specific histidine-rich glycoprotein polymorphism on male infertility and semen parameters

Lindgren

Nordqvist

Kårehed

et al. 2016

Reproductive BioMedicine Online

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In women, there is evidence that a single nucleotide polymorphism (SNP) in the histidine-rich glycoprotein (HRG) named HRG C633T is relevant for a number of fertility outcomes including recurrent miscarriage, ovarian response and pregnancy outcome after IVF. This case-control study was designed to investigate whether the HRG C633T SNP is important for male infertility and pregnancy rate following IVF. Cases were 139 infertile couples and controls were 196 pregnant couples. The 335 couples all contributed with one blood sample per partner. Genomic DNA was extracted and genotyping was performed using a TaqMan® SNP Genotyping Assay. Information on pregnancy rate and semen parameters was derived from medical records. Infertile couples in which the male partner was a homozygous carrier of the HRG C633T SNP had significantly lower (P < 0.01) pregnancy rate following IVF in comparison with couples where the male partner was a heterozygous HRG C633T SNP carrier. Male homozygous HRG 633T SNP carriers had overall lower total sperm count, sperm concentration, motility score and yield after preparation. In conclusion, once infertility is established the HRG C633T SNP seems to be important for male infertility and pregnancy rate following IVF.

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Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

The effect of a specific histidine-rich glycoprotein polymorphism on male infertility and semen parameters

Lindgren

Nordqvist

Kårehed

et al. 2016

Reproductive BioMedicine Online

View full text Add to dashboard Cite

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“…() and/or by Massart et al . (), while five genes were recently associated with non‐obstructive azoospermia (Ayhan et al ., ; Ge et al ., ; Yatsenko et al ., ; Miyamoto et al ., ). The coding regions and exon‐intron boundaries of the target genes were analyzed by NGS‐based amplicon sequencing.…”

Section: Methodsmentioning

confidence: 99%

“…reviewed previous studies and each compiled a list of genes associated with idiopathic non‐obstructive azoospermia (Massart et al ., ; Miyamoto et al ., ). Subsequently, several other genes including TEX11 have been reported as possible causes of azoospermia (Ayhan et al ., ; Ge et al ., ; Yatsenko et al ., ; Miyamoto et al ., ). However, there has been no report of comprehensive mutation screening of these genes; therefore, the clinical significance of monogenic mutations in the etiology of idiopathic non‐obstructive azoospermia remains uncertain (Mitchell et al ., ).…”

Section: Introductionmentioning

confidence: 99%

Next‐generation sequencing for patients with non‐obstructive azoospermia: implications for significant roles of monogenic/oligogenic mutations

et al. 2017

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Azoospermia affects up to 1% of adult men. Non-obstructive azoospermia is a multifactorial disorder whose molecular basis remains largely unknown. To date, mutations in several genes and multiple submicroscopic copy-number variations (CNVs) have been identified in patients with non-obstructive azoospermia. The aim of this study was to clarify the contribution of nucleotide substitutions in known causative genes and submicroscopic CNVs in the genome to the development of non-obstructive azoospermia. To this end, we conducted sequence analysis of 25 known disease-associated genes using next-generation sequencing and genome-wide copy-number analysis using array-based comparative genomic hybridization. We studied 40 Japanese patients with idiopathic non-obstructive azoospermia. Functional significance of molecular alterations was assessed by in silico analyses. As a result, we identified four putative pathogenic mutations, four rare polymorphisms possibly associated with disease risk, and four probable neutral variants in 10 patients. These sequence alterations included a heterozygous splice site mutation in SOHLH1 and a hemizygous missense substitution in TEX11, which have been reported as causes of non-obstructive azoospermia. Copy-number analysis detected five X chromosomal or autosomal CNVs of unknown clinical significance, in addition to one known pathogenic Y chromosomal microduplication. Five patients carried multiple molecular alterations. The results indicate that monogenic and oligogenic mutations, including those in SOHLH1 and TEX11, account for more than 10% of cases of idiopathic non-obstructive azoospermia. Furthermore, this study suggests possible contributions of substitutions in various genes as well as submicroscopic CNVs on the X chromosome and autosomes to non-obstructive azoospermia, which require further validation.

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“…Spermatogenesis is followed by the differentiation of primordial germ cells into motile spermatozoa. This process is controlled by numerous factors [23, 24], and disruption of these factors may affect the quality and quantity of spermatozoa production and fertility in males. Many genes have been associated with spermatogenesis, but the pathophysiological mechanisms of these genes have not been elucidated.…”

Section: Discussionmentioning

confidence: 99%

Sequence variations of the EGR4 gene in Korean men with spermatogenesis impairment

et al. 2017

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Background Egr4 is expressed in primary and secondary spermatocytes in adult mouse testes and has a crucial role in regulating germ cell maturation. The functional loss of Egr4 blocks spermatogenesis, significantly reducing the number of spermatozoa that are produced. In this study, we examined whether EGR4 variants are present in Korean men with impaired spermatogenesis.MethodsA total 170 Korean men with impaired spermatogenesis and 272 normal controls were screened. The coding regions including exon-intron boundaries of EGR4 were sequenced by PCR-direct sequencing method.ResultsWe identified eight sequence variations in the coding region and 3′-UTR regions of the EGR4 gene. Four were nonsynonymous variants (rs771189047, rs561568849, rs763487015, and rs546250227), three were synonymous variants (rs115948271, rs528939702, and rs7558708), and one variant (rs2229294) was localized in the 3′-UTR. Three nonsynonymous variants [c.65_66InsG (p. Cys23Leufs*37), c.236C > T (p. Pro79Leu), c.1294G > T (p. Val432Leu)] and one synonymous variant [c.1230G > A (p. Thr410)] were not detected in controls. To evaluate the pathogenic effects of nonsynonymous variants, we used seven prediction methods. The c.214C > A (p. Arg72Ser) and c.236C > T (p. Pro79Leu) variants were predicted as “damaging” by SIFT and SNAP2. The c.65_66insG (p. Cys23Leufs*37) variants were predicted as “disease causing” by Mutation Taster, SNPs &GO and SNAP2. The c.867C > G (p. Leu289) variants were predicted as “disease causing” only by Mutation Taster.ConclusionTo date, this study is the first to screen the EGR4 gene in relation to male infertility. However, our findings did not clearly explain how nonsynonymous EGR4 variations affect spermatogenesis. Therefore, further studies are required to validate the functional impact of EGR4 variations on spermatogenesis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-017-0408-5) contains supplementary material, which is available to authorized users.

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Associations of single nucleotide polymorphisms in the Pygo2 coding sequence with idiopathic oligospermia and azoospermia

Cited by 6 publications

References 34 publications

The effect of a specific histidine-rich glycoprotein polymorphism on male infertility and semen parameters

The effect of a specific histidine-rich glycoprotein polymorphism on male infertility and semen parameters

Next‐generation sequencing for patients with non‐obstructive azoospermia: implications for significant roles of monogenic/oligogenic mutations

Sequence variations of the EGR4 gene in Korean men with spermatogenesis impairment

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