The association of four SNPs in DNA mismatch repair genes with idiopathic male infertility in northwest China

Zhao, Xinyan; Mu, Chunlan; Ma, Jia; Dai, Xiaoling; Hu, Jiao

doi:10.1111/iji.12448

Cited by 10 publications

(7 citation statements)

References 45 publications

(58 reference statements)

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“…Mismatch repair proteins involved in meiosis are identified, including MLH1, MLH3 and MSH4 [25] . Gene knockout mice reveal that MLH1 greatly influence infertility in female mice [26] .…”

Section: Discussionmentioning

confidence: 99%

Prediction key genes and the potential molecular mechanism for early recurrent pregnancy loss by Multi-Omics analysis

Huang

Wei

Zhang

et al. 2020

Preprint

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BackgroundThe potential mechanism of early recurrent pregnancy loss (ERPL) has not been fully elucidated, a multi-omics analysis can help us find key genes.ResultsWe download data from Gene Expression Omnibus (GEO), 90 hypermethylation-down regulated genes and 49 hypomethylation-up regulated genes were identified by intersection. Compared with the normal early pregnancy group, the expression of ERCC2 and MLH1 was lower in ERPL group, but the expression of PLEK and FOS was higher, and the expression of MLH1 was statistically significant (p<0.05). Compared with the anembryonic (empty sac) miscarriage group, the expression of MLH1, PLEK, FOS decreased, and that of ERCC2 increased in the embryonic miscarriage group. TF-MDEGs networks predicted SP1, POLR2A, YY1, CREM and CREB1 were involved in methylation regulation of DNA promoter with MDEGs. Among them, YY1, FOXP3 and p53 may be related to the mechanism of MLH1 in ERPL.ConclusionsOur study identified possible aberrant MDEGs, and TF- MDEGs regulatory networks may be related to its mechanism. MLH1 may play an important role in early embryonic development.

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“…Mismatch repair proteins involved in meiosis are identified, including MLH1, MLH3 and MSH4 [25] . Gene knockout mice reveal that MLH1 greatly influence infertility in female mice [26] .…”

Section: Discussionmentioning

confidence: 99%

Prediction key genes and the potential molecular mechanism for early recurrent pregnancy loss by Multi-Omics analysis

Huang

Wei

Zhang

et al. 2020

Preprint

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“…One of the DNA repair systems correcting mispaired bases during DNA replication errors is mismatch repair (MMR). Allelic variants in MMR MSH genes can be responsible for the MMR failure in sperm DNA and male infertility [ 60 , 61 , 62 ]. The rs26279 variant in MSH3 is associated with idiopathic male infertility, which makes it a possible risk factor for idiopathic male infertility [ 62 ].…”

Section: Reasons and Consequences Of Genome Instabilitymentioning

confidence: 99%

“…Allelic variants in MMR MSH genes can be responsible for the MMR failure in sperm DNA and male infertility [ 60 , 61 , 62 ]. The rs26279 variant in MSH3 is associated with idiopathic male infertility, which makes it a possible risk factor for idiopathic male infertility [ 62 ]. The MSH3 gene located at 5q11-13 encodes an MSH3 protein playing an essential role in the MMR system.…”

Section: Reasons and Consequences Of Genome Instabilitymentioning

confidence: 99%

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Idiopathic Infertility as a Feature of Genome Instability

Puzuka

Alksere

Gailīte

et al. 2021

Life

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Genome instability may play a role in severe cases of male infertility, with disrupted spermatogenesis being just one manifestation of decreased general health and increased morbidity. Here, we review the data on the association of male infertility with genetic, epigenetic, and environmental alterations, the causes and consequences, and the methods for assessment of genome instability. Male infertility research has provided evidence that spermatogenic defects are often not limited to testicular dysfunction. An increased incidence of urogenital disorders and several types of cancer, as well as overall reduced health (manifested by decreased life expectancy and increased morbidity) have been reported in infertile men. The pathophysiological link between decreased life expectancy and male infertility supports the notion of male infertility being a systemic rather than an isolated condition. It is driven by the accumulation of DNA strand breaks and premature cellular senescence. We have presented extensive data supporting the notion that genome instability can lead to severe male infertility termed “idiopathic oligo-astheno-teratozoospermia.” We have detailed that genome instability in men with oligo-astheno-teratozoospermia (OAT) might depend on several genetic and epigenetic factors such as chromosomal heterogeneity, aneuploidy, micronucleation, dynamic mutations, RT, PIWI/piRNA regulatory pathway, pathogenic allelic variants in repair system genes, DNA methylation, environmental aspects, and lifestyle factors.

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“…Finally, Sato and colleagues in a GWAS conducted in the Japanese population reported an additional risk variant [18]. In addition to GWAS, several gene candidate studies have been conducted analyzing infertility parameters as outcomes [19][20][21][22][23][24]. Considering that male infertility is a common condition and almost half of the cases are idiopathic, the discovery of novel genetic variants is of the utmost importance to further our knowledge on this field of research.…”

Section: Introductionmentioning

confidence: 99%

Telomere Length and Male Fertility

Gentiluomo

Luddi

Cingolani

et al. 2021

IJMS

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Over the past decade, telomeres have attracted increasing attention due to the role they play in human fertility. However, conflicting results have been reported on the possible association between sperm telomere length (STL) and leukocyte telomere length (LTL) and the quality of the sperm parameters. The aim of this study was to run a comprehensive study to investigate the role of STL and LTL in male spermatogenesis and infertility. Moreover, the association between the sperm parameters and 11 candidate single nucleotide polymorphisms (SNPs), identified in the literature for their association with telomere length (TL), was investigated. We observed no associations between sperm parameters and STL nor LTL. For the individual SNPs, we observed five statistically significant associations with sperm parameters: considering a p < 0.05. Namely, ACYP2˗rs11125529 and decreased sperm motility (p = 0.03); PXK˗rs6772228 with a lower sperm count (p = 0.02); NAF1˗rs7675998 with increased probability of having abnormal acrosomes (p = 0.03) and abnormal flagellum (p = 0.04); ZNF208˗rs8105767 and reduction of sperms with normal heads (p = 0.009). This study suggests a moderate involvement of telomere length in male fertility; however, in our analyses four SNPs were weakly associated with sperm variables, suggesting the SNPs to be pleiotropic and involved in other regulatory mechanisms independent of telomere homeostasis, but involved in the spermatogenic process.

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The association of four SNPs in DNA mismatch repair genes with idiopathic male infertility in northwest China

Cited by 10 publications

References 45 publications

Prediction key genes and the potential molecular mechanism for early recurrent pregnancy loss by Multi-Omics analysis

Prediction key genes and the potential molecular mechanism for early recurrent pregnancy loss by Multi-Omics analysis

Idiopathic Infertility as a Feature of Genome Instability

Telomere Length and Male Fertility

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