Increased de novo DNA Methylation Enzymes in Sperm of Individuals with Varicocele

(Pages: 389-396)
Moloud Rashidi, M.Sc, 1,2Marziyeh Tavalaee, Ph.D, 1Homayon Abbasi, M.D, 3Michail Nomikos, Ph.D, 4Mohammad Hossein Nasr-Esfahani, Ph.D, 1,3,*
Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
Department of Biology, Faculty of Science, NourDanesh Institute of Higher Education, Isfahan, Iran
Isfahan Fertility and Infertility Center, Isfahan, Iran
College of Medicine, Member of QU Health, Qatar University, Doha, Qatar
Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
Department of Biology, Faculty of Science, NourDanesh Institute of Higher Education, Isfahan, Iran
Isfahan Fertility and Infertility Center, Isfahan, Iran
College of Medicine, Member of QU Health, Qatar University, Doha, Qatar
*Corresponding Address: P.O.Box: 8159358686 Department of Animal Biotechnology Reproductive Biomedicine Research Center Royan Institute for Biotechnology ACECR Isfahan Iran Email:mh.nasr-esfahani@royaninstitute.org
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Rashidi Moloud, Tavalaee Marziyeh, Abbasi Homayon, Nomikos Michail, Nasr-Esfahani Mohammad Hossein. Increased de novo DNA Methylation Enzymes in Sperm of Individuals with Varicocele. Cell J. 2021; 23(4): 389-396.

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.