The Association between the Altered Levels of H3K9ac and H3K9me2 Histone Marks in Transition Protein and Protamine Genes with Impaired Spermatogenesis

Document Type : Original Article (s)

Authors

1 Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, Academic Center for Education, Culture and Research, Tehran, Iran

2 Assistant Professor, Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, Academic Center for Education, Culture and Research, Tehran, Iran

3 Professor, Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, Academic Center for Education, Culture and Research AND Department of Urology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

4 Associate Professor, Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, Academic Center for Education, Culture and Research, Tehran, Iran

Abstract

Background: Successful spermatogenesis requires a series of tightly controlled epigenetic events leads to condensation of sperm chromatin. Through these epigenetic events, expression of transition nuclear proteins (TNPs) and protamines (PRMs) rise to replace with histones. Many epigenetic factors are involved in regulation of these genes. Therefore, evaluation of histone modifications e.g. H3K9ac and H3K9me2, as powerful epigenetic tool in regulation of mentioned genes, can represent better insight into molecular mechanisms of infertility.Methods: The consent was obtained from 60 azoospermic infertile men referred to Royan Institute, Tehran, Iran, according local ethical approval. Then, based on spermogram and pathological features of patients, testes tissue samples were collected from three groups including complete maturation arrest, sertoli cell only syndrome, and hypospermatogenesis (as positive control). Expression of TNPs and PRMs were evaluated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Besides, chromatin immunopercipitation (ChIP) coupled with real time- polymerase chain reaction was performed to evaluate the incorporation of H3K9ac and H3K9me2 into regulatory regions of mentioned genes.Findings: There was a significant decrease in expression of TNP and PRM genes in two groups of spermatogenic failure in comparison to positive control. These findings also confirmed by chromatin immunopercipitation data which revealed decreased incorporation of H3K9ac (activating mark), and increased incorporation of H3K9me2 (repression mark) into regulatory regions of mentioned genes in complete maturation arrest and sertoli cell only syndrome groups vs. positive control.Conclusion: These finding implies significant association of histone modifications with altered expression of sperm chromatin condensing genes and impairment of spermatogenesis in male infertility.

Keywords

References

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Journal of Isfahan Medical School
Volume 36, Issue 473 - Serial Number 473
March and April 2018
Pages 277-283

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History

  • Receive Date: 25 November 2017
  • Revise Date: 03 May 2024
  • Accept Date: 06 April 2022

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