Genome-wide differential methylation analyses identifies methylation signatures of male infertility
| Autor: | Rajesh Pandey, Singh Rajender, Vertika Singh, Kiran Singh, Sameer Trivedi, Gopal Gupta, Saumya Sarkar, Neeraj K. Agrawal, Kumar Mohanty Sujit |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Male Biology Genome Deep sequencing Male infertility 03 medical and health sciences medicine Humans Spermatogenesis Gene Infertility Male Genetics Sperm Count Rehabilitation EZH2 Obstetrics and Gynecology Methylation Oligospermia DNA Methylation medicine.disease 030104 developmental biology Reproductive Medicine Case-Control Studies DNA methylation Sperm Motility CpG Islands Genomic imprinting Genome-Wide Association Study |
| Zdroj: | Human reproduction (Oxford, England). 33(12) |
| ISSN: | 1460-2350 |
| Popis: | Study question Do methylation changes in sperm DNA correlate with infertility? Study answer Loss of spermatogenesis and fertility was correlated with 1680 differentially-methylated CpGs (DMCs) across 1052 genes. What is known already Methylation changes in a number of genes have been correlated with reduced sperm count and motility. Study design, size, duration This case-control study used spermatozoal DNA from 38 oligo-/oligoastheno-zoospermic infertile patients and 26 normozoospermic fertile men. Participants/materials, settings, methods Genome-wide methylation analysis was undertaken using 450 K BeadChip on spermatozoal DNA from six infertile and six fertile men to identify DMCs. This was followed by deep sequencing of spermatozoal DNA from 32 infertile patients and 20 fertile controls. Main results and the role of chance A total of 1680 DMCs were identified, out of which 1436 were hypermethylated and 244 were hypomethylated. Classification of DMCs according to the genes identified BCAN, CTNNA3, DLGAP2, GATA3, MAGI2 and TP73 among imprinted genes, SPATA5, SPATA7, SPATA16 and SPATA22 among spermatogenesis-associated genes, KDM4C and JMJD1C, EZH2 and HDAC4 among genes which regulate methylation and gene expression, HLA-C, HLA-DRB6 and HLA-DQA1 among complementation and immune response genes, and CRISPLD1, LPHN3 and CPEB2 among other genes. Genes showing significant differential methylation in deep sequencing, i.e. HOXB1, GATA3, EBF3, BCAN and TCERG1L, are strong candidates for further investigations. The role of chance was ruled out by deep sequencing of select genes. Large-scale data N/A. Limitations, reason for caution Genome-wide analyses are fairly accurate, but may not be exactly validated in replication studies across all DMCs. We used the 't' test in the genome-wide methylation analysis, whereas other tests could provide a more robust and powerful analysis. Wider implications of the findings DMCs can serve as markers for inclusion in infertility screening panels, particularly those in the genes showing differential methylation consistent with previous studies. The genes validated by deep sequencing are strong candidates for investigations of their roles in spermatogenesis. Study funding/competing interest(s) The study was funded by the Council of Scientific and Industrial Research (CSIR), Govt. of India with grant number BSC0101 awarded to Rajender Singh. None of the authors has any competing interest to declare. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|