Methylation levels of<i>IGF2</i>and<i>KCNQ1</i>in spermatozoa from infertile men are associated with sperm DNA damage

Ni, Wuhua; Pan, Chengshuang; Pan, Qiongqiong; Fei, Qianjin; Huang, Xuefeng; Zhang, Chenyu

doi:10.1111/and.13239

Cited by 21 publications

(11 citation statements)

References 71 publications

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“…Accordingly, ROS have been found capable of altering H19-Igf2 methylation (by reducing H19 and increasing Igf2 methylation pattern) [32]. Moreover, abnormal methylation of the imprinted genes IGF2 and KCNQ1 at the spermatozoon level has recently been reported in infertile patients, in association with an increased sperm DNA fragmentation [33]. Furthermore, global sperm DNA methylation has been shown to inversely correlate with sperm DNA fragmentation [34].…”

Section: Sperm Genomementioning

confidence: 99%

Molecular Biology of Spermatogenesis: Novel Targets of Apparently Idiopathic Male Infertility

Cannarella

Condorelli

Mongioì

et al. 2020

IJMS

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Male infertility affects half of infertile couples and, currently, a relevant percentage of cases of male infertility is considered as idiopathic. Although the male contribution to human fertilization has traditionally been restricted to sperm DNA, current evidence suggest that a relevant number of sperm transcripts and proteins are involved in acrosome reactions, sperm-oocyte fusion and, once released into the oocyte, embryo growth and development. The aim of this review is to provide updated and comprehensive insight into the molecular biology of spermatogenesis, including evidence on spermatogenetic failure and underlining the role of the sperm-carried molecular factors involved in oocyte fertilization and embryo growth. This represents the first step in the identification of new possible diagnostic and, possibly, therapeutic markers in the field of apparently idiopathic male infertility.

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Section: Sperm Genomementioning

confidence: 99%

Molecular Biology of Spermatogenesis: Novel Targets of Apparently Idiopathic Male Infertility

Cannarella

Condorelli

Mongioì

et al. 2020

IJMS

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“…However, other studies exploring the methylation levels of IGF2 in spermatozoa offer inconclusive data. Ni et al 18 associated lower IGF2 methylation levels with higher sperm DNA fragmentation (negative correlation), whereas Darbandi et al 46 positively correlated these with ROS levels. Additionally, ROS levels were positively correlated with the DNA fragmentation index 46 .…”

Section: Discussionmentioning

confidence: 99%

“…The field of human reproduction is no exception in following this trend, as studying epigenetic changes in gametes is even more interesting considering that gametes are responsible for transferring genetic material to the next generation 11 . Lately, a number of studies exploring sperm DNA methylation from different angles have been published, 12‐18 but there is a lack of studies on how different sperm preparation methods could possibly influence the sperm DNA methylation profile. To our knowledge, only one study has explored the DNA methylation profile of spermatozoa after DGC sperm preparation, 22 which is one of the most often used sperm preparation method in assisted reproduction 23 .…”

Section: Discussionmentioning

confidence: 99%

“…Consequently, this can affect the outcome of in vitro fertilization (IVF) procedures in terms of abnormal embryogenesis and pregnancy rates 13,14 . In studies on sperm DNA methylation, whole‐genome methylation analysis can be performed 13‐15 but often, only particular regions or genes are examined exclusively, for instance, regions and genes that are known to have specific paternal or maternal imprinting 16‐18 . Thus, these genes or regions are expressed only from one parental allele and around 100 such imprints have been found in mammalian genomes 19 …”

Section: Introductionmentioning

confidence: 99%

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Minor DNA methylation changes are observed in spermatozoa prepared using different protocols

Štimpfel

Vrtačnik-Bokal

2020

Andrology

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Background DNA methylation patterns can show transgenerational inheritance and are influenced by lifestyle and environmental factors. It is suggested that these patterns can be changed by assisted reproductive technology. Objectives To evaluate the impact of two different sperm preparation methods, conventional density gradient centrifugation (DGC) vs. density gradient centrifugation followed by magnetic‐activated cell sorting (MACS) of non‐apoptotic spermatozoa, on sperm DNA methylation profile. Materials and methods We analyzed semen of patients included in our IVF treatment program. Half of the semen from each included patient was prepared for ICSI using the DGC method and the other half with DGC followed by MACS. The remaining samples were processed for DNA methylation analysis with reduced representation bisulfite sequencing (RRBS). In addition to the DNA methylation profile, we assessed the morphology and DNA fragmentation of spermatozoa. Results RRBS analysis revealed that the average genome‐wide methylation level was similar between both groups (DGC vs. MACS group) and ranged from 0.53 to 0.56. Furthermore, RRBS analysis identified 99 differentially methylated regions (DMRs) and 800 differentially methylated positions (DMPs). In the DGC group, 43 DMRs and 392 DMPs were hypermethylated whereas 56 DMRs and 408 DMPs were hypomethylated compared with those in the MACS group. When DMRs and DMPs were annotated to genes, 3 genes associated with imprinting were found: IGF2, PRDM16, and CLF4/BRUNOL4. The percentage of morphologically normal spermatozoa (MACS vs. DGC; 14.0 ± 10.8 vs. 13.2 ± 10.0; P = .335) and of spermatozoa with fragmented DNA of patients with RRBS analysis (22.9 ± 21.1% vs. 34.4 ± 21.2; P = .529) were also similar between groups. Discussion and Conclusion Although the average genome‐wide level of sperm DNA methylation was similar in both sample groups, a distinctive number of methylation changes were observed in DMR and DMP levels. A larger number of samples should be analyzed and additional sperm preparation methods should be tested to confirm our findings.

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“…Poplinski et al [29] conclude that low sperm counts were clearly associated with IGF2/H19 ICR1 hypomethylation, and idiopathic male infertility was strongly associated with imprinting defects at IGF2/H19 ICR1. Ni et al [30] indicated that the aberrant methylation of IGF2 and KCNQ1 gene may be associated with sperm DNA damage. Tang et al [31] revealed that miR-210 was involved in spermatogenesis by targeting IGF2 in male infertility.…”

Section: Discussionmentioning

confidence: 99%

RNA-sequencing and bioinformatics analysis of long noncoding RNAs and mRNAs in the asthenozoospermia

Lü

Wang

et al. 2020

Bioscience Reports

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Asthenozoospermia is one of the major causes of human male infertility. Long non-coding RNAs (lncRNAs) play critical roles in the spermatogenesis processes. This study aims to investigate the intricate regulatory network associated with asthenozoospermia. The lncRNAs expression profile was analyzed in the asthenozoospermia seminal plasma exosomes by RNA-sequencing, and the functions of differentially expressed genes (DEGs) were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and DO (Disease Ontology) enrichment analyses. Pearson’s correlation test was utilized to calculate the correlation coefficients between lncRNA and mRNAs. Moreover, the lncRNA-miRNA-mRNA co-expression network was constructed with bioinformatics. From the co-expression analyses, we identified the cis regulated correlation pairs lncRNAs-mRNAs. To confirm sequencing results with five of the identified DElncRNAs were verified with quantitative reverse-transcription polymerase chain reaction (qRT-PCR). We identified 4,228 significantly DEGs, 995 known DElncRNAs, 2,338 DEmRNAs and 11,706 novel DElncRNAs between asthenozoospermia and normal group. GO and KEGG analyses showed that the DEGs were mainly associated with metabolism, transcription, ribosome and channel activity. We found 254,981 positive correlations lncRNA-mRNA pairs through correlation analysis. The detailed lncRNA-miRNA-mRNA regulatory network included 11 lncRNAs, 35 miRNAs and 59 mRNAs. From the co-expression analyses, we identified 7 cis-regulated correlation pair lncRNAs-mRNAs. Additionally, the qRT-PCR analysis confirmed our sequencing results. Our study constructed the lncRNA-mRNA-miRNA regulation networks in asthenozoospermia. Therefore, the study findings provide a set of pivotal lncRNAs for future investigation into the molecular mechanisms of asthenozoospermia.

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Methylation levels ofIGF2andKCNQ1in spermatozoa from infertile men are associated with sperm DNA damage

Cited by 21 publications

References 71 publications

Molecular Biology of Spermatogenesis: Novel Targets of Apparently Idiopathic Male Infertility

Molecular Biology of Spermatogenesis: Novel Targets of Apparently Idiopathic Male Infertility

Minor DNA methylation changes are observed in spermatozoa prepared using different protocols

RNA-sequencing and bioinformatics analysis of long noncoding RNAs and mRNAs in the asthenozoospermia

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