Aberrations in sperm DNA methylation patterns are associated with abnormalities in semen parameters of subfertile males

Laqqan, Mohammed M.; Solomayer, Erich‐Franz; Hammadeh, Mohamad Eid

doi:10.1016/j.repbio.2017.05.010

Cited by 28 publications

(16 citation statements)

References 62 publications

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“…Moreover, six CpGs (CpG3, CpG5, CpG6*, CpG8, CpG9 and CpG10) of eleven, related to the cg19406113 site amplicon, showed a significant difference in DNA methylation between the case and control groups. These findings are in accordance with previous ones noted by other researchers (Aston et al., ; Jenkins et al., ; Laqqan, Solomayer, & &Hammadeh, ), who found an alteration in the sperm DNA methylation levels between subfertile and fertile males.…”

Section: Discussionsupporting

confidence: 93%

DNA methylation level of spermatozoa from subfertile and proven fertile and its relation to standard sperm parameters

et al. 2018

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The epigenetic mechanism plays an important role in spermatogenesis such as DNA methylation where this episode is represented by either switching genes on or off. Twenty-eight samples (14 case and 14 controls) were subjected to Infinium 450K BeadChip arrays to identify genomic regions that differ in sperm DNA methylation patterns in the subfertile compared to the proven fertile group. Then two CpGs were validated by deep bisulphite sequencing on 82 sperm samples. The results screening study revealed eight CpGs were significantly different in their sperm DNA methylation levels between cases and control group. The results of the validation study for the two CpGs (cg19779893 and cg19406113) showed that a significant variation in the methylation level at 2 CpGs of 3 CpGs related to cg19779893 site amplicon in cases compared to the controls. Moreover, six CpGs related to the cg19406113 site amplicon showed significant differences in sperm DNA methylation between the cases and the control group. Furthermore, there was a significant decrease in the sperm parameters in the cases compared to the control group. This study found two CpGs altered in their sperm DNA methylation levels. In addition, a strong association was found between changes in the sperm DNA methylation levels in these CpGs sites and sperm parameters.

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Section: Discussionsupporting

confidence: 93%

DNA methylation level of spermatozoa from subfertile and proven fertile and its relation to standard sperm parameters

et al. 2018

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“…Deformity in DNA methylation of the spermatozoa is related with abberation in the semen parameters leading to the reduced sperm count, low volume of semen, decreased motility and reduced sperm vitality of subfertile males. Studies have shown that DNA methylation of spermatozoa may be associated with infertility in couples (Laqqan, Solomayer, & Hammadeh, ).…”

Section: Dna Methylationmentioning

confidence: 99%

Epigenetics and oxidative stress: A twin‐edged sword in spermatogenesis

et al. 2019

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Spermatogenesis is a series of complex events involving a delicate balance between cell proliferation and cell differentiation. Aggregation of chromatins and epigenetic modifications play a vital role in spermatogenesis via regulation of molecular pathways to maintain testicular homeostasis. These epigenetic mechanisms consist of histone modification, chromatin remodelling, DNA methylation and miRNA, etc., which reportedly are critical players in spermatogenesis. One such mechanism involves regulation of oxidative stress in the male reproductive system. The fact that testicular cells contain plenty of unsaturated fatty acids and undergo division at a high rate makes spermatogenic cells highly susceptible to oxidative insult leading to deleterious effect on spermatozoa, which may culminate in infertility in men. Although the correlation between ROS‐mediated oxidative stress and epigenetic alterations has been indicated, research in this regard is still in infancy. Further, the fact that environmental and life style factors are critical determinants of spermatogenic potential indicates the importance of epigenetic regulation of key molecular events in spermatogenesis. Therefore, the current review aims to discuss the ROS‐induced epigenetic deregulation of the molecular mechanism(s) involved in spermatogenesis.

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“…Aberrations in sperm DNA methylation have also been shown to be associated with abnormalities in semen parameters (low sperm count, decreased volume of semen, reduced progressive motility, high percentage of immotile sperm lowered sperm vitality) of subfertile males that were trying to conceive for at least 10 years (Laqqan et al 2017a). The authors of this study identified that DNA methylation was consistently different at a small number of CpGs between proven fertile males and subfertile case subjects, using Infinium Human Methylation 450 K BeadChip arrays, validating previous findings using local deep bisulfite sequencing (Gries et al 2013).…”

Section: Dna Methylationmentioning

confidence: 99%

“…Although infertility can be attributed to decreased semen quality, testicular dysfunction, infections of the genital tract and known genetic disorders (such as single-gene alterations and chromosomal abnormalities) (Krausz et al 2015), a number of male patients suffer from a condition known as idiopathic or unexplained male infertility (UMI), in which the aetiology is poorly understood (Urdinguio et al 2015). Given the major genome reprogramming events that occur during gametogenesis and early development, in recent years, a number of studies have pointed towards aberrant epigenetic reprogramming of the genome as a potential contributory factor to male infertility (O'Doherty & McGettigan 2014, Laurentino et al 2015, Stuppia et al 2015, Urdinguio et al 2015, Schagdarsurengin & Steger 2016, Kropp et al 2017, Laqqan et al 2017a, Nasri et al 2017. It should be stressed that, at present, direct associations between epigenetic changes and infertility are unclear -it is indeed possible that they are simply correlated with changes in infertility and not causal.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic reprogramming during spermatogenesis and male factor infertility

McSwiggin¹,

O’Doherty²

2018

Reproduction

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Infertility is an often devastating diagnosis encountered by around one in six couples who are trying to conceive. Moving away from the long-held belief that infertility is primarily a female issue, it is now recognised that half, if not more, of these cases may be due to male factors. Recent evidence has suggested that epigenetic abnormalities in chromatin dynamics, DNA methylation or sperm-borne RNAs may contribute to male infertility. In light of advances in deep sequencing technologies, researchers have been able to increase the coverage and depth of sequencing results, which in turn has allowed more comprehensive analyses of spermatozoa chromatin dynamics and methylomes and enabled the discovery of new subsets of sperm RNAs. This review examines the most current literature related to epigenetic processes in the male germline and the associations of aberrant modifications with fertility and development.

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Aberrations in sperm DNA methylation patterns are associated with abnormalities in semen parameters of subfertile males

Cited by 28 publications

References 62 publications

DNA methylation level of spermatozoa from subfertile and proven fertile and its relation to standard sperm parameters

DNA methylation level of spermatozoa from subfertile and proven fertile and its relation to standard sperm parameters

Epigenetics and oxidative stress: A twin‐edged sword in spermatogenesis

Epigenetic reprogramming during spermatogenesis and male factor infertility

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