USP7 and SET9 Expression in The Oligospermic Human Semen: A Case-Control Study

Document Type : Original Article

Authors

Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran

Abstract

Background: Oligospermia is defined as a less than 15 million per milliliter sperm in each ejaculation of semen. Proper and complete spermatogenesis requires the expression of a large number of genes. As a result, stopping the expression of any of them may lead to disrupt the process of spermatogenesis. In order to understand the disorders of spermatogenesis, it is necessary to study expression of effective genes in the spermatogenesis process. Therefore, in the present study, USP7 and SET9 (SETD7) gene expression was examined in the healthy and oligospermic men.
Materials and Methods: In this case-control study, semen samples of individuals with normal sperm and oligospermia were collected from men who referred to the Roya Clinic (Qom, Iran) according to World Health Organization (WHO) parameters after obtaining consent. Then the expression of USP7 and SET9 genes in two groups was analyzed using quantitative polymerase chain reaction (qPCR).
Results: There was no difference forage between the healthy and oligospermic individuals (P=0.889). The data showed that, USP7 gene expression in the patients was 3.99 times higher than the control group (P<0.001). The expression of SET9 gene in the patient was 1.28 times less than the control group, which was not significant (P=0.231). The results indicated that USP7 gene expression was increased in the 84% of oligospermic individuals.
Conclusion: The USP7 gene can be considered as one of the molecular markers in the development of oligospermia.

Keywords


1. Patel AS, Leong JY, Ramasamy R. Prediction of male infertility by the World Health Organization laboratory manual for assessment of semen analysis: a systematic review. Arab J Urol. 2018; 16(1): 96-102.
2. Morshed-Behbahani B, Lamyian M, Joulaei H, Rashidi BH, Montazeri A. Infertility policy analysis: a comparative study of selected lower middle-middle-and high-income countries. Global Health. 2020; 16(1): 1-9.
3. Gumus E, Kati B, Pelit ES, Ordek E, Ciftci H. A different look at genetic factors in individuals with non-obstructive azoospermia or oligospermia in our research study: to whom, which threshold, when, in what way? Rev Int Androl. 2021; 19(1): 41-48.
4. Luo M, Zhou J, Leu NA, Abreu CM, Wang J, Anguera MC, et al. Polycomb protein SCML2 associates with USP7 and counteracts histone H2A ubiquitination in the XY chromatin during male meiosis. PLoS Genet. 2015; 11(1): e1004954.
5. Shen Y, Tu W, Liu Y, Yang X, Dong Q, Yang B, et al. TSPY1 suppresses USP7-mediated p53 function and promotes spermatogonial proliferation. Cell Death Dis. 2018; 9(5): 1-4.
6. Sinha D, Kalimutho M, Bowles J, Chan AL, Merriner DJ, Bain AL, et al. Cep55 overexpression causes male-specific sterility in mice by suppressing Foxo1 nuclear retention through sustained activation of PI3K/Akt signaling. FASEB J. 2018; 32(9): 4984-4999.
7. Gunes S, Esteves SC. Role of genetics and epigenetics in male infertility. Andrologia. 2021; 53(1): e13586.
8. Wang Z, Kang W, You Y, Pang J, Ren H, Suo Z, et al. USP7: novel drug target in cancer therapy. Front Pharmacol. 2019; 10: 427.
9. Huang P, Zhou Z, Shi F, Shao G, Wang R, Wang J, et al. Effects of the IGF-1/PTEN/Akt/FoxO signaling pathway on male reproduction in rats subjected to water immersion and restraint stress. Mol Med Rep. 2016; 14(6): 5116-5124.
10. Samanta L, Swain N, Ayaz A, Venugopal V, Agarwal A. Post-translational modifications in sperm proteome: the chemistry of proteome diversifications in the pathophysiology of male factor infertility. Biochim Biophys Acta. 2016; 1860(7): 1450-1465.
11. Pozhidaeva A, Bezsonova I. USP7: Structure, substrate specificity, and inhibition. DNA Repair (Amst). 2019; 76: 30-39.
12. Crowe SO, Rana AS, Deol KK, Ge Y, Strieter ER. Ubiquitin chain enrichment middle-down mass spectrometry enables characterization of branched ubiquitin chains in cellulo. Anal Chem. 2017; 89(8): 4428-4434.
13. Jesenberger V, Jentsch S. Deadly encounter: ubiquitin meets apoptosis. Nat Rev Mol Cell Biol. 2002; 3(2): 112-121.
14. Wojcik C, Benchaib M, Lornage J, Czyba JC, Guerin JF. Proteasomes in human spermatozoa. Int J Androl. 2000; 23(3): 169-177.
15. Kim RQ, Sixma TK. Regulation of USP7: a high incidence of E3 complexes. J Mol Biol. 2017; 429(22): 3395-3408.
16. Ozkocer SE, Konac E. The current perspective on genetic and epigenetic factors in sperm maturation in the epididymis. Andrologia. 2021; 53(3): e13989.
17. Cannarella R, Condorelli RA, Mongioì LM, La Vignera S, Calogero AE. Molecular biology of spermatogenesis: novel targets of apparently idiopathic male infertility. Inter J Mol Sci. 2020; 21(5): 1728.
18. Brohi RD, Huo LJ. Posttranslational modifications in spermatozoa and effects on male fertility and sperm viability. Omics. 2017; 21(5): 245-256.
19. Li X, Yao Z, Yang D, Jiang X, Sun J, Tian L, et al. Cyanidin-3-O-glucoside restores spermatogenic dysfunction in cadmium-exposed pubertal mice via histone ubiquitination and mitigating oxidative damage. J Hazard Mater. 2020; 387: 121706.