The role of epigenetics in idiopathic male infertility

Güneş, Sezgin; Arslan, Mehmet Alper; Hekim, Neslihan; Aşçı, Ramazan

doi:10.1007/s10815-016-0682-8

Cited by 106 publications

(83 citation statements)

References 136 publications

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“…In conclusion, DNA methylation has been closely associated with male infertility (66,121). Understanding the mechanisms underlying DNA methylation is particularly important in order to develop therapeutic strategies for male genital system diseases caused by abnormal sperm DNA methylation.…”

Section: Resultsmentioning

confidence: 98%

“…Using restriction landmark genomic scanning technology, DNA methylation was detected for chromosomes 6, 20 and 22 in spermatozoa, with numerous sites in sperm and somatic cells exhibiting varying degrees of methylation (66)(67)(68). The extent of methylation in sperm cells was significantly increased, as compared with fibroblasts (>20%), liver cells (10%), and CD4 + and CD8 + lymphocytes (5%) (68,69 (65,69,70).…”

Section: Dna Methylation and Spermatogenesismentioning

confidence: 99%

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DNA methylation in spermatogenesis and male infertility

Cui¹,

Xuan

Wu³

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Infertility is a significant problem for human reproduction, with males and females equally affected. However, the molecular mechanisms underlying male infertility remain unclear. Spermatogenesis is a highly complex process involving mitotic cell division, meiosis cell division and spermiogenesis; during this period, unique and extensive chromatin and epigenetic modifications occur to bring about specific epigenetic profiles in spermatozoa. It has recently been suggested that the dysregulation of epigenetic modifications, in particular the methylation of sperm genomic DNA, may serve an important role in the development of numerous diseases. The present study is a comprehensive review on the topic of male infertility, aiming to elucidate the association between sperm genomic DNA methylation and poor semen quality in male infertility. In addition, the current status of the genetic and epigenetic determinants of spermatogenesis in humans is discussed. Contents1. Introduction 2. DNA methylation 3. DNA methylation and spermatogenesis 4. DNA methylation and genomic imprinting 5. DNA methylation and male infertility 6. Conclusion IntroductionEpigenetics is the study of genomic structural modifications that affect gene expression without altering the underlying nucleotide sequence (1-3). Epigenetic mechanisms involved in the regulation of gene expression include the regulation of non-coding RNA, chromatin remodeling, DNA methylation and histone modifications (4,5). Of these mechanisms, DNA methylation has been implicated in numerous biological functions, such as the development of spermatozoa and early embryos, and the repression of endogenous retrotransposons, while it also has a wide range of effects in gene expression (2,3,6). The dysregulation of DNA methylation has previously been associated with various human disorders, and has been shown to increase the risk of fertilization failure, dysfunction in embryogenesis, perinatal mortality, congenital abnormalities, preterm birth and low birth weight (7-11). The present review assesses the significance of DNA methylation in spermatogenesis in order to elucidate the association between the dysregulation of DNA methylation and male infertility. This may provide a basis for the prevention and treatment of male infertility, as well as permit the evaluation of the epigenetic quality of sperm in order to reduce the risk of epigenetic diseases in cases where conception is performed by assisted reproductive technology (ART). DNA methylationEpigenetic mechanisms are critical regulators of gene expression during spermatogenesis that may influence male fertility (12-14). Cytosine, a key DNA base, is methylated at the position, typically in the context of CpG dinucleotides. The methylation of constitutive heterochromatic and promoter regions is generally associated with reduced gene transcription (Fig. 1A) (15-18). Therefore, DNA methylation is a type of epigenetic modification that can effectively promote gene silencing (Fig. 1B). The methyl group for this chemical modif...

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Section: Resultsmentioning

confidence: 98%

Section: Dna Methylation and Spermatogenesismentioning

confidence: 99%

DNA methylation in spermatogenesis and male infertility

Cui¹,

Xuan

Wu³

et al. 2016

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

“…With ICSI, individual sperm are then selected visually based on motility and morphology by a trained embryologist for injection to an egg 7, 8. However, other important sperm attributes that can affect ART outcomes, including sperm DNA–chromatin or chromosomal integrity, mutational, or methylome composition, and the presence of reactive oxygen species (ROS)9, 10, 11, 12, 13, 14, 15, 16, 17 are typically not considered. In particular, long periods of incubation, as well as shear stresses due to centrifugation, increase ROS accumulation.…”

Section: Introductionmentioning

confidence: 99%

Guidance and Self‐Sorting of Active Swimmers: 3D Periodic Arrays Increase Persistence Length of Human Sperm Selecting for the Fittest

et al. 2017

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Male infertility is a reproductive disease, and existing clinical solutions for this condition often involve long and cumbersome sperm sorting methods, including preprocessing and centrifugation‐based steps. These methods also fall short when sorting for sperm free of reactive oxygen species, DNA damage, and epigenetic aberrations. Although several microfluidic platforms exist, they suffer from structural complexities, i.e., pumps or chemoattractants, setting insurmountable barriers to clinical adoption. Inspired by the natural filter‐like capabilities of the female reproductive tract for sperm selection, a model‐driven design, featuring pillar arrays that efficiently and noninvasively isolate highly motile and morphologically normal sperm, with lower epigenetic global methylation, from raw semen, is presented. The Simple Periodic ARray for Trapping And isolatioN (SPARTAN) created here modulates the directional persistence of sperm, increasing the spatial separation between progressive and nonprogressive motile sperm populations within an unprecedentedly short 10 min assay time. With over 99% motility of sorted sperm, a 5‐fold improvement in morphology, 3‐fold increase in nuclear maturity, and 2–4‐fold enhancement in DNA integrity, SPARTAN offers to standardize sperm selection while eliminating operator‐to‐operator variations, centrifugation, and flow. SPARTAN can also be applied in other areas, including conservation ecology, breeding of farm animals, and design of flagellar microrobots for diagnostics.

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“…Moreover, the abnormalities in the DNA methylation patterns and histone modification of spermatozoa contribute in the decline of male fecundity which has been identified in 15%-30% of infertile problems in male Jenkins, Aston, Meyer et al, 2016;Soubry, 2015). Interestingly, several of previous studies have revealed a correlation between epigenetic alterations and infertility problems in male (Gunes, Arslan, Hekim, & Asci, 2016;Tian et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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

Laqqan

Hammadeh

2017

Andrologia

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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.

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The role of epigenetics in idiopathic male infertility

Cited by 106 publications

References 136 publications

DNA methylation in spermatogenesis and male infertility

DNA methylation in spermatogenesis and male infertility

Guidance and Self‐Sorting of Active Swimmers: 3D Periodic Arrays Increase Persistence Length of Human Sperm Selecting for the Fittest

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

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