Bing Song1,2,3,4,5, Chao Wang1,2,3,4,5, Yujie Chen1, Guanjian Li1, Yang Gao1, Fuxi Zhu1,2,3,4,5, Huan Wu1,2,3,4,5, Mingrong Lv1,2,3,4,5, Ping Zhou1,2,3,4,5, Zhaolian Wei1,2,3,4,5, Xiaojin He6,7,8,9,10, Yunxia Cao11,12,13,14,15. 1. Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China. 2. NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, Hefei, 230032, China. 3. Ministry of Education Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Hefei, 230032, China. 4. Anhui Province Key Laboratory of Reproductive Health and Genetics, Hefei, 230032, China. 5. Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, Hefei, 230032, China. 6. Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China. hxj0117@126.com. 7. NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, Hefei, 230032, China. hxj0117@126.com. 8. Ministry of Education Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Hefei, 230032, China. hxj0117@126.com. 9. Anhui Province Key Laboratory of Reproductive Health and Genetics, Hefei, 230032, China. hxj0117@126.com. 10. Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, Hefei, 230032, China. hxj0117@126.com. 11. Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China. caoyunxia6@126.com. 12. NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, Hefei, 230032, China. caoyunxia6@126.com. 13. Ministry of Education Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Hefei, 230032, China. caoyunxia6@126.com. 14. Anhui Province Key Laboratory of Reproductive Health and Genetics, Hefei, 230032, China. caoyunxia6@126.com. 15. Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, Hefei, 230032, China. caoyunxia6@126.com.
Abstract
PURPOSE: To evaluate the association between the DNA methylation of specific genes and sperm DNA integrity status in human sperm samples. METHODS: A total of 166 semen samples were evaluated (86 controls and 80 cases with impaired sperm DNA integrity). We detected the methylation status of 257 CpG sites among two imprinted genes (H19 and SNRPN) and four non-imprinted genes related to male infertility (MTHFR, GSTM1, DAZL, and CREM) by using a targeted next-generation sequencing method. RESULTS: Differential methylation was found in 43 CpG sites of the promoters of the six candidate genes. H19, SNRPN, MTHFR, DAZL, GSTM1, and CREM contained 22, 12, 1, 4, 0, and 4 differentially methylated CpG sites (P<0.05), respectively. The imprinting genes were associated with relatively higher rates of differentially methylated CpG sites (28.21% in H19 and 41.38% in SNRPN) than the non-imprinting genes. One CpG site in H19 remained significant after performing strict Bonferroni correction. CONCLUSION: In this study, we found that different site-specific DNA methylation signatures were correlated with sperm DNA integrity status. Further studies are needed to investigate the specific mechanisms leading to the epigenetic modifications.
PURPOSE: To evaluate the association between the DNA methylation of specific genes and sperm DNA integrity status in human sperm samples. METHODS: A total of 166 semen samples were evaluated (86 controls and 80 cases with impaired sperm DNA integrity). We detected the methylation status of 257 CpG sites among two imprinted genes (H19 and SNRPN) and four non-imprinted genes related to male infertility (MTHFR, GSTM1, DAZL, and CREM) by using a targeted next-generation sequencing method. RESULTS: Differential methylation was found in 43 CpG sites of the promoters of the six candidate genes. H19, SNRPN, MTHFR, DAZL, GSTM1, and CREM contained 22, 12, 1, 4, 0, and 4 differentially methylated CpG sites (P<0.05), respectively. The imprinting genes were associated with relatively higher rates of differentially methylated CpG sites (28.21% in H19 and 41.38% in SNRPN) than the non-imprinting genes. One CpG site in H19 remained significant after performing strict Bonferroni correction. CONCLUSION: In this study, we found that different site-specific DNA methylation signatures were correlated with sperm DNA integrity status. Further studies are needed to investigate the specific mechanisms leading to the epigenetic modifications.
Authors: Gerald F Cox; Joachim Bürger; Va Lip; Ulrike A Mau; Karl Sperling; Bai-Lin Wu; Bernhard Horsthemke Journal: Am J Hum Genet Date: 2002-05-08 Impact factor: 11.025
Authors: Trevor G Cooper; Elizabeth Noonan; Sigrid von Eckardstein; Jacques Auger; H W Gordon Baker; Hermann M Behre; Trine B Haugen; Thinus Kruger; Christina Wang; Michael T Mbizvo; Kirsten M Vogelsong Journal: Hum Reprod Update Date: 2009-11-24 Impact factor: 15.610