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Unraveling epigenomic abnormality in azoospermic human males by WGBS, RNA-Seq, and transcriptome profiling analyses

Abstract

Purpose

To determine associations between genomic DNA methylation in testicular cells and azoospermia in human males.

Methods

This was a case-control study investigating the differences and conservations in DNA methylation, genome-wide DNA methylation, and bulk RNA-Seq for transcriptome profiling using testicular biopsy tissues from NOA and OA patients. Differential methylation and different conserved methylation regions associated with azoospermia were identified by comparing genomic DNA methylation of testicular seminiferous cells derived from NOA and OA patients.

Results

The genome methylation modification of testicular cells from NOA patients was disordered, and the reproductive-related gene expression was significantly different.

Conclusion

Our findings not only provide valuable knowledge of human spermatogenesis but also paved the way for the identification of genes/proteins involved in male germ cell development. The approach presented in this report provides a powerful tool to identify responsible biomolecules, and/or cellular changes (e.g., epigenetic abnormality) that induce male reproductive dysfunction such as OA and NOA.

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Authors’ roles

S.F and C.Y.C conceived and designed the study. C.X and J.F collected the sample. XL.W and CH.L performed the experiments. LF.H and YM.C analyzed and interpreted the data. XL.W wrote the manuscript and S.F and C.Y.C revised the manuscript. All authors discussed the results and implications of the study.

Funding

This work was supported by The National Key Research and Development Program of China (2018YFC1003500 to F.S), The National Natural Science Foundation of China (81671510 to F.S), and The Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX19_2027).

Author information

Correspondence to C. Yan Cheng or Fei Sun.

Ethics declarations

The experiments using human materials were approved by Nantong University. Informed consent was obtained from all human subjects.

Conflict of interest

The authors declare that they have no conflicts of interest.

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Wu, X., Luo, C., Hu, L. et al. Unraveling epigenomic abnormality in azoospermic human males by WGBS, RNA-Seq, and transcriptome profiling analyses. J Assist Reprod Genet (2020). https://doi.org/10.1007/s10815-020-01716-7

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Keywords

  • Non-obstructive azoospermia (NOA)
  • Obstructive azoospermia (OA)
  • DNA methylation
  • Bulk transcriptome