• PMID: 30373665
• Gene Name: H19
• Condition: Idiopathic male infertility
• Association: Associated
• Population size: 135
• Population details: 135 (normozoospermia (n?=?39), moderate oligozoospermia (n?=?45), and severe oligozoospermia (n?=?51), and fertile controls (n?=?59))
• Sex: Male
• Infertility type: Male infertility
• Associated genes: NGS (Methylation pattern)

Idiopathic male infertility is strongly associated with aberrant DNA methylation of imprinted loci in sperm: a case-control study

Tang Q, Pan F, Yang J, Fu Z, Lu Y, Wu X, Han X, Chen M, Lu C, Xia Y, Wang X, Wu W.

BACKGROUND: Male infertility is a complex disease caused by a combination of genetic, environmental, and lifestyle factors. Abnormal epigenetic programming has been proposed as a possible mechanism compromising male fertility. Recent studies suggest that aberrant imprinting in spermatozoa in a subset of infertile men is a risk factor for congenital diseases in children conceived via assisted reproduction techniques. In this study, we examined the DNA methylation status of CpG sites within the differentially methylated regions (DMRs) of three imprinted genes, H19, GNAS, and DIRAS3, using combined bisulfite PCR restriction analysis and bisulfite sequencing in sperm obtained from 135 men with idiopathic male infertility, including normozoospermia (n = 39), moderate oligozoospermia (n = 45), and severe oligozoospermia (n = 51), and fertile controls (n = 59). The percentage of global methylation was compared between fertile controls and infertile patients displaying abnormal DNA methylation status of imprinted loci. Moreover, we also analyzed whether the DNA methyltransferases (DNMTs) polymorphisms impact upon the methylation patterns of imprinted genes in idiopathic infertile males. RESULTS: Aberrant methylation patterns of imprinted genes were more prevalent in idiopathic infertile males, especially in patients with oligozoospermia. Infertile males with aberrant methylation patterns of imprinted genes displayed a tendency of lower global methylation levels, although not reaching statistical significance (P = 0.13). In the genotype-epigenotype correlation analysis, no significant association was observed between aberrant methylation patterns of the three imprinted genes and genotypes of the four DNA methyltransferase (DNMT) genes. CONCLUSION: We conclude that abnormalities of DMR within imprinted genes may be associated with idiopathic male infertility. Disruption in methylation pattern of the three imprinted genes does not occur in high-risk genotypes of DNMTs. FAU - Tang, Qiuqin AU - Tang Q AD - Department of Obstetrics, The Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China. FAU - Pan, Feng AU - Pan F AD - Department of Urology, The Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China. FAU - Yang, Jing AU - Yang J AD - State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, China. AD - Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China. FAU - Fu, Ziqiang AU - Fu Z AD - State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, China. AD - Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China. FAU - Lu, Yiwen AU - Lu Y AD - State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, China. AD - Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China. FAU - Wu, Xian AU - Wu X AD - National Toxicology Program Laboratory, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. FAU - Han, Xiumei AU - Han X AD - State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, China. AD - Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China. FAU - Chen, Minjian AU - Chen M AD - State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, China. AD - Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China. FAU - Lu, Chuncheng AU - Lu C AD - State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, China. AD - Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China. FAU - Xia, Yankai AU - Xia Y AD - State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, China. AD - Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China. FAU - Wang, Xinru AU - Wang X AD - State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, China. AD - Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.