Array-based DNA methylation profiling reveals peripheral blood differential methylation in male infertility

Sarkar, Saumya; Sujit, Kumar Mohanty; Singh, Vertika; Pandey, Rajesh; Trivedi, Sameer; Singh, Kiran; Gupta, Gopal; Rajender, Singh

doi:10.1016/j.fertnstert.2019.03.020

Cited by 22 publications

(18 citation statements)

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“…We provided evidence in a recent study that methylation changes in sperm DNA correlate with infertility and could provide markers for quality check of spermatozoa before assisted reproduction . Some of these markers could even be traced into the peripheral blood, making their scoring easier …”

Section: Discussionmentioning

confidence: 80%

Increased DNA methylation in the spermatogenesis‐associated (SPATA) genes correlates with infertility

et al. 2020

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| INTRODUC TI ONHuman male infertility affects approximately 15%-20% of couples worldwide 1 with male factors contributing to about half of them. [2][3][4] A significant proportion of male infertility remains idiopathic, where the underlying molecular mechanisms have not been worked out. 5,6 Studies in the last one decade have demonstrated that apart from genetic variations contributing, epigenetic alterations also make a significant contribution to male infertility. Epigenetic changes may in fact play a highly significant role as they are subject to a number of environmental factors, lifestyle, and nutrition. DNA methylation is one of the most important epigenetic phenomena, which plays a critical role in germ cell development and differentiation. Indeed, it is required for correct DNA compaction in sperm head and to permanently silence Abstract Background: Spermatogenesis-associated (SPATA) family of genes plays important roles in spermatogenesis, sperm maturation or fertilization. The knockout studies in mice have demonstrated that SPATA genes are crucial for fertility. Gene expression and genetic polymorphism studies have further suggested their correlation with infertility; however, methylation analysis of SPATA genes in human male infertility has not yet been undertaken.Objectives: To analyze the methylation status of SPATA4, SPATA5 and SPATA6 genes in oligozoospermic male infertility. Materials and methods:In the present study, we have analyzed DNA methylation pattern in the promoter regions of SPATA4, SPATA5 and SPATA6 genes in oligozoospermic patients and compared it with normozoospermic fertile controls. Semen samples were obtained from 30 oligozoospermic infertile and 19 normozoospermic fertile controls, and DNA methylation levels of the target gene promoters were analyzed by amplicon based deep sequencing methylation analysis using MiSeq.Results: SPATA4 (P < 0.0008), SPATA5 (P = 0.009) and SPATA6 (Promoter, P < 0.0005; Exon 1, P = 0.0128) genes were significantly hypermethylated in oligozoospermic patients in comparison to controls. This is the first study reporting a higher methylation in the promoters of SPATA4, SPATA5 and SPATA6 in oligozoospermic infertile individuals in comparison to the normozoospermic fertile controls.Discussion: Altered methylation of SPATA genes would affect pathways involved in sperm production or affect various processes linked to sperm fertility. Conclusion:In conclusion, hypermethylation in the SPATA4, SPATA5 and SPATA6 genes correlates with oligozoospermic infertility. K E Y W O R D SSPATA genes, male infertility, oligozoospermia, spermatozoa, DNA methylation | 603 SUJIT eT al.

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Section: Discussionmentioning

confidence: 80%

Increased DNA methylation in the spermatogenesis‐associated (SPATA) genes correlates with infertility

et al. 2020

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“…As high-throughput approaches are able to detect extensive variations in epigenetic marks, DNA methylation changes could potentially be used as a diagnostic tool to predict the risk of both male infertility and male infertility-related diseases (Aston et al, 2015;Fang et al, 2019;Patel et al, 2020). For instance, an array-based DNA methylation profile conducted on peripheral blood has revealed variations in DNA methylation patterns in infertile males compared to normozoospermic fertile controls, suggesting that epigenome-based blood markers can be used for diagnostic purposes (Sarkar et al, 2019). This has also been suggested by the results of another high-throughput study focused on congenital hypopituitarism (CH), which is a pituitary gland hormone deficiency that leads to metabolic disorders and male reproductive dysfunction.…”

Section: High-throughput Techniques For Dna Methylome Investigationmentioning

confidence: 99%

“…New functional studies on this topic are needed to better elucidate the mechanisms affecting methylation in sperm. Nevertheless, extensive knowledge of sperm DNA methylation status in association with reduced reproductive capability is useful in developing novel diagnostic tools for male infertility (Balasubramanian et al, 2019;Sarkar et al, 2019). The current primary diagnostic protocol for identifying infertile males relies on the assessment of sperm number, motility, and morphology.…”

Section: Future Perspectivesmentioning

confidence: 99%

Epigenetics of Male Infertility: The Role of DNA Methylation

Rotondo

Lanzillotti

Mazziotta

et al. 2021

Front. Cell Dev. Biol.

102

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In recent years, a number of studies focused on the role of epigenetics, including DNA methylation, in spermatogenesis and male infertility. We aimed to provide an overview of the knowledge concerning the gene and genome methylation and its regulation during spermatogenesis, specifically in the context of male infertility etiopathogenesis. Overall, the findings support the hypothesis that sperm DNA methylation is associated with sperm alterations and infertility. Several genes have been found to be differentially methylated in relation to impaired spermatogenesis and/or reproductive dysfunction. Particularly, DNA methylation defects of MEST and H19 within imprinted genes and MTHFR within non-imprinted genes have been repeatedly linked with male infertility. A deep knowledge of sperm DNA methylation status in association with reduced reproductive potential could improve the development of novel diagnostic tools for this disease. Further studies are needed to better elucidate the mechanisms affecting methylation in sperm and their impact on male infertility.

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“…A more recent study conducted with peripheral blood samples of normozoospermic fertile and oligo/azoospermic men using 450K array has revealed significant differences between the study and control groups. Additionally, novel candidate genes were reported to play an important role in the pathophysiology of spermatogenesis and fertility (Sarkar et al, 2019).…”

Section: Methylation Characteristicsmentioning

confidence: 99%

Role of genetics and epigenetics in male infertility

Güneş

Esteves

2020

Andrologia

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Male infertility is a heterogeneous and common condition that might be a result of genetic or epigenetic variations or both. The frequency of genetic aberrations in azoospermic or severely oligozoospermic men is at least 15%, and the major genetic causes are karyotype abnormalities, microdeletions on Y chromosome, and mutations of cystic fibrosis transmembrane conductance regulator (CFTR) (Hamada, Esteves, & Agarwal, 2013; Hotaling & Carrell, 2014). Beyond these widely accepted genetic causes, a number of both autosomal and particularly X-chromosomal genes are associated with male infertility (Ropke & Tuttelmann, 2017). Furthermore, epigenetic control of gene expression plays a crucial role in both sperm function and fertilising ability (Gunes, Arslan, Hekim, & Asci, 2016a). Epigenetic regulation might be changed by external and internal factors or both, including environmental factors, nutrition and stress (Gunes, 2018b). This review summarises the latest evidence concerning the role of genetics and epigenetics on male infertility. 1.1 | Overview of human genome and genetics The haploid human genome consists of about 3 billion letters (3.3 billion nucleotides) distributed in 24 chromosomes. However, only 1.5% of the human genome encodes a protein (Gregory & Gilbert, 2005; Maher, 2012). The human genome project (HGP) has shown that genomes of nonrelated people exhibit a single base variation in every 1,200-1,500 DNA bases. These variations are

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Array-based DNA methylation profiling reveals peripheral blood differential methylation in male infertility

Cited by 22 publications

References 70 publications

Increased DNA methylation in the spermatogenesis‐associated (SPATA) genes correlates with infertility

Increased DNA methylation in the spermatogenesis‐associated (SPATA) genes correlates with infertility

Epigenetics of Male Infertility: The Role of DNA Methylation

Role of genetics and epigenetics in male infertility

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