Alterations in DNA methylation patterns and gene expression in spermatozoa of subfertile males

Abstract

This study was designed to evaluate the DNA methylation patterns and gene expression in spermatozoa from subfertile males. Thirty samples were subjected to 450K arrays as a screening study to evaluate the variation in sperm DNA methylation levels between cases and controls groups, and then three CpG sites (cg07227024, cg05813498 and cg23081194) have the highest difference in methylation levels and located within ALS2CR12, GAA and UBE2G2 genes respectively; these were selected for further analysis using deep bisulphite sequencing and qPCR in 136 samples (64 proven fertile males "controls" and 72 subfertile males "cases"). A significant difference in the methylation level was found between cases and controls at two CpGs, six CpGs and three CpGs in ALS2CR12, GAA and UBE2G2 gene-related amplicon respectively. Besides, the qPCR results showed a significant change in the expression levels of GAA, UBE2G2 and ALS2CR12 gene in cases compared to the controls (p ≤ .00001). In conclusion, the methylation levels at CpGs in GAA, UBE2G2 and ALS2CR12 gene amplicons were significantly different in subfertile compared to proven fertile males. In addition, a significantly different was showed in the expression levels of GAA, UBE2G2 and ALS2CR12 genes in subfertile males compared to proven fertile males.

Retracted:Influence of variation in global sperm DNA methylation level on the expression level of protamine genes and human semen parameters

“…On the other hand, these results observed a significant variation and down-regulation in the protamine genes expression levels among the study groups and these results are lined with other studies that presented a reduction in the RNA expression level between normospermia and oligospermia groups, and this decline associated with specific genes involved in the spermatogenesis process and sperm functions (Laqqan & Hammadeh, 2018b;Montjean et al, 2012). Besides, another study showed a significant variation in protamine content within the spermatozoa of oligospermia group compared to normospermia group (Aoki, Emery, Liu, et al, 2006).…”

“…Indeed, DNA methylation is considered as a fundamental regulator of transcription in spermatozoa and the aberrations in the methylation process maybe lead to defects in the gene expression and this is what was observed in the males who have abnormalities in semen parameters (Laqqan & Hammadeh, 2018b;Montjean et al, 2012).…”

“…Emerging data found the association between the sperm DNA fragmentation, embryo death and the reduction in the level of protamine 2 (Cho et al, 2003). Recently, the epigenetic studies observed a relationship between the change in the sperm DNA methylation patterns and the expression level of protamine genes which affects semen parameters (Chen, Yan, & Duan, 2016;Consales et al, 2014;Laqqan & Hammadeh, 2018b). Accordingly, the current study was designed (a) to evaluate if there is a variation in the status of global sperm DNA methylation among the study groups (normospermia, oligospermia and proved fertile), (b) to assess whether there is a variation on the expression level of protamine genes (protamine 1 and protamine 2) among the study groups and (c) to study the association between the variation in the sperm global DNA methylation level and protamine expression level at spermatozoa and the other semen parameters.…”

Methylation of the SNRPN gene in infertile men without mutations in common candidate genes for reduced fertility

“…Тем не менее полученные данные свидетельствуют в пользу того, что аберрантное метилирование импринтированных генов может быть вовлечено в патогенез более 11 % случаев мужского бесплодия без учета тех случаев, которые связаны с высокопенетрантными мутациями и сочетаниями неблагоприятных полиморфизмов в известных генах-кандидатах бесплодия. Для более точной оценки доли эпигенетической патологии в структуре молекулярных Многие исследователи продолжают поиск дифференциально метилированных генов, которые могут быть вовлечены в патогенез олигозооспермии, в частности, показана повышенная частота метилирования генов GAA, UBE2G2 и ALS2CR12 у пациентов с олигозооспермией относительно контрольной группы (p <0,0001) [33]. Выполненный в настоящей работе комплексный анализ мутаций и полиморфизмов в совокупности с оценкой частоты аберрантного метилирования SNRPN демонстрирует, что 20,4 % (10 / 49) случаев в гетерогенной выборке мужчин с бесплодием связаны со структурными генетическими нарушениями и / или эпигенетической патологией.…”

>b<Estudo do perfil proteico e epigenético do núcleo espermático bovino com influência na produção >i<in vitro>/i< de embriões>/b<

“…Studies in human described differences for methylation profile between fertile and subfertile men (ASTON et al, 2015;LAQQAN;HAMMADEH, 2018;NASRI et al, 2017). The methylation profile on CpGs sites within imprinted control regions like H19 gene may serve as epigenomic biomarker of infertility in men (PENG et al, 2018).…”