Reproductive Biology and Endocrinology (Nov 2022)

Poor semen parameters are associated with abnormal methylation of imprinted genes in sperm DNA

  • Bing Song,
  • Yujie Chen,
  • Chao Wang,
  • Guanjian Li,
  • Zhaolian Wei,
  • Xiaojin He,
  • Yunxia Cao

DOI
https://doi.org/10.1186/s12958-022-01028-8
Journal volume & issue
Vol. 20, no. 1
pp. 1 – 7

Abstract

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Abstract Background Altered sperm DNA methylation patterns of imprinted genes as well as certain spermatogenesis-related genes has been proposed as a possible mechanism of male subfertility. Some reports suggest that there is an elevated risk of congenital diseases, associated with imprinted genes, in children conceived via intra-cytoplasmic sperm injection, due to the involvement of spermatozoa with aberrant imprinted genes obtained from infertile men. Methods In this study, the DNA methylation status of the promoter regions of six imprinted genes, namely potassium voltage-gated channel subfamily Q member 1 (KCNQ1), maternally expressed gene 3 (MEG3), insulin-like growth factor 2 (IGF-2), KCNQ1 overlapping transcript 1 (KCNQ1OT1), mesoderm specific transcript (MEST), and paternally expressed gene 3 (PEG3), were detected by a next generation sequencing-based multiple methylation-specific polymerase chain reaction analysis of sperm samples obtained from 166 men who sought fertility evaluation in our Reproductive Medicine Center. Thereafter, the semen samples were classified into subgroups according to sperm motility and DNA integrity status. Results As compared to the normozoospermic group, the samples of the asthenospermic group exhibited significant hypermethylation in two CpG sites of IGF-2 and significant hypomethylation in one CpG site of KCNQ1 as well as three CpG sites of MEST (P 0.05). Additionally, we found that 111 of 323 CpG sites were hypomethylated in the group with DNA fragmentation index (DFI) ≥ 30% as compared to the group with DFI 0.05). Hence, aberrant methylation patterns of imprinted genes were more prevalent in males with poor sperm quality, especially in those with severe sperm DNA damage. Conclusion In conclusion, abnormal DNA methylation of some CpG sites of imprinted genes are associated with poor sperm quality, including asthenospermia and severe sperm DNA impairment.

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