Increased De Novo DNA Methylation Enzymes in Sperm of Individuals with Varicocele

Overview

Journal Cell J

Specialty Cell Biology

Date 2021 Aug 29

PMID 34455713

Citations 5

Authors

Moloud Rashidi

Marziyeh Tavalaee

Homayon Abbasi

Michail Nomikos

Mohammad Hossein Nasr-Esfahani

Affiliations

Soon will be listed here.

Abstract

Objective: Chronic genital heat-stress associated with varicocele leads to DNA hypo-methylation of spermatozoa. The objective of this study was comparing level of DNA methyl-transferases (DNMTs) in sperm of men suffering varicocele with fertile individuals.

Materials And Methods: In this case-control study, semen samples were obtained from 35 infertile men with varicocele (grade II or III) and 26 fertile men. Sperm parameters were assessed according to World Health Organization (WHO) protocol. DNMTs enzymes level were assessed by flow cytometer and fluorescence microscope. mRNAs expression of these DNMTs were also assessed by real-time reverse transcription polymerase chain reaction (RT-PCR).

Results: DNMT1 and DNMT3A proteins were mainly localized in equatorial and mid-piece regions of sperm head, respectively, while DNMT3B protein appeared to be localized mainly in equatorial and anterior regions of sperm head. In contrast to DNMT1, expression and percentage of DNMT3A and DNMT3B at RNA and protein levels were significantly higher in the varicocele group compared to the fertile group (P<0.05). In addition, significant correlations were found between sperm concentration and motility as well as DNMT1 and DNMT3B proteins levels in the infertile individuals with varicocele (P<0.05). Additionally, significant correlations were observed between abnormal sperm morphology with DNMTs proteins in the infertile individuals with varicocele.

Conclusion: Unlike DNMT1, which is involved in maintenance of DNA methylation at both RNA and protein levels, expression of de novo methylation enzymes (DNMT3A and DNMT3B) at both levels were increased in the varicocele group compared to the fertile group. Based on literature, this increase might be due to the dual roles played by DNMT3A and DNMT3B, as methyl-transferases in normal condition as well as dehydroxymethylases in stress condition, like varicocele. Although, this hypothesis needs further validation.

Citing Articles

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The Evolving Landscape of Male Varicocele Pathophysiology in the Era of Multi-Omics: A Narrative Review of the Current Literature.

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Aberrant Expression of TET2 Accounts for DNA Hypomethylation in Varicocele.

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Down-Regulated Expression of Cystathionine β-Synthase and Cystathionine γ-Lyase in Varicocele, and Infertile Men: A Case-Control Study.

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