Idiopathic male infertility is strongly associated with aberrant DNA methylation of imprinted loci in sperm: a case-control study
Abstract 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...
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| Format: | Article |
| Language: | English |
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BMC
2018-10-01
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| Series: | Clinical Epigenetics |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13148-018-0568-y |
| _version_ | 1819007057045487616 |
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| author | Qiuqin Tang Feng Pan Jing Yang Ziqiang Fu Yiwen Lu Xian Wu Xiumei Han Minjian Chen Chuncheng Lu Yankai Xia Xinru Wang Wei Wu |
| author_facet | Qiuqin Tang Feng Pan Jing Yang Ziqiang Fu Yiwen Lu Xian Wu Xiumei Han Minjian Chen Chuncheng Lu Yankai Xia Xinru Wang Wei Wu |
| author_sort | Qiuqin Tang |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-21T00:18:31Z |
| format | Article |
| id | doaj.art-0cf180682cda4783a793ba6343135aa5 |
| institution | Directory Open Access Journal |
| issn | 1868-7075 1868-7083 |
| language | English |
| last_indexed | 2024-12-21T00:18:31Z |
| publishDate | 2018-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Clinical Epigenetics |
| spelling | doaj.art-0cf180682cda4783a793ba6343135aa52022-12-21T19:22:09ZengBMCClinical Epigenetics1868-70751868-70832018-10-0110111010.1186/s13148-018-0568-yIdiopathic male infertility is strongly associated with aberrant DNA methylation of imprinted loci in sperm: a case-control studyQiuqin Tang0Feng Pan1Jing Yang2Ziqiang Fu3Yiwen Lu4Xian Wu5Xiumei Han6Minjian Chen7Chuncheng Lu8Yankai Xia9Xinru Wang10Wei Wu11Department of Obstetrics, The Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care HospitalDepartment of Urology, The Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care HospitalState Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical UniversityState Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical UniversityState Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical UniversityNational Toxicology Program Laboratory, Division of the National Toxicology Program, National Institute of Environmental Health SciencesState Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical UniversityState Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical UniversityState Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical UniversityState Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical UniversityState Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical UniversityState Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical UniversityAbstract 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.http://link.springer.com/article/10.1186/s13148-018-0568-yDNA methylationDNMTGlobal methylationImprinted geneMale infertilityPolymorphism |
| spellingShingle | Qiuqin Tang Feng Pan Jing Yang Ziqiang Fu Yiwen Lu Xian Wu Xiumei Han Minjian Chen Chuncheng Lu Yankai Xia Xinru Wang Wei Wu Idiopathic male infertility is strongly associated with aberrant DNA methylation of imprinted loci in sperm: a case-control study Clinical Epigenetics DNA methylation DNMT Global methylation Imprinted gene Male infertility Polymorphism |
| title | Idiopathic male infertility is strongly associated with aberrant DNA methylation of imprinted loci in sperm: a case-control study |
| title_full | Idiopathic male infertility is strongly associated with aberrant DNA methylation of imprinted loci in sperm: a case-control study |
| title_fullStr | Idiopathic male infertility is strongly associated with aberrant DNA methylation of imprinted loci in sperm: a case-control study |
| title_full_unstemmed | Idiopathic male infertility is strongly associated with aberrant DNA methylation of imprinted loci in sperm: a case-control study |
| title_short | Idiopathic male infertility is strongly associated with aberrant DNA methylation of imprinted loci in sperm: a case-control study |
| title_sort | idiopathic male infertility is strongly associated with aberrant dna methylation of imprinted loci in sperm a case control study |
| topic | DNA methylation DNMT Global methylation Imprinted gene Male infertility Polymorphism |
| url | http://link.springer.com/article/10.1186/s13148-018-0568-y |
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