Pro-inflammatory Cytokines and MicroRNAs in Male Infertility

Overview

Journal Mol Biol Rep

Specialty Molecular Biology

Date 2021 Jul 28

PMID 34319544

Citations 7

Authors

Hana Attia

Federica Finocchi

Monia Orciani

Meriem Mehdi

Ines Zidi Jrah

Raffaella Lazzarini

Giancarlo Balercia

Monica Mattioli Belmonte

Affiliations

Soon will be listed here.

Abstract

Background: Male infertility is a problem that affects 10-15% of men of reproductive age. In particular, gametogenesis is a complex process in which inflammation may play a central role through the secretion of cytokines and the expression of microRNAs. We assessed the potential role of proinflammatory cytokines (TNF-α, IL-6 and IL-1α) and microRNAs (miR-146a-5p, miR-34a-5p and miR-23a-3p) in the seminal plasma of infertile men compared to controls, evaluating their correlation with seminal and biochemical parameters.

Methods And Results: Expression of cytokines and microRNAs was analyzed by ELISA and q-PCR. Our data shows that IL-1α was significantly increased in the azoospermic group compared to controls, TNF-α mRNA was more expressed in the oligozoospermic group than controls. There were no significant differences in miRNAs expression among the three groups. The correlations between sperm parameters and inflammatory markers were evaluated, however no significance was highlighted.

Conclusions: The determination of each inflammatory marker separately in the seminal plasma of subfertile men, despite some significant differences, does not have a diagnostic value in male infertility even if an assay of selective pro-inflammatory cytokines and microRNAs in the semen may improve the diagnosis of male infertility.

Citing Articles

Causal inference of inflammatory proteins in infertility: a Mendelian randomization study.

Chen P, Ni S, Ou-Yang L Front Endocrinol (Lausanne). 2025; 16:1448530.

PMID: 40070583 PMC: 11893426. DOI: 10.3389/fendo.2025.1448530.

Understanding the Associations of Urogenital Microbiomes With Fertility and In Vitro Fertilization.

Berard A, Brubaker D, Nemecio D, Farr Zuend C Am J Reprod Immunol. 2025; 93(2):e70035.

PMID: 39945201 PMC: 11822749. DOI: 10.1111/aji.70035.

Effects of empagliflozin on gonadal functions of hyperglycemic male wistar rats.

Bdeir R, Al-Sawalha N, Al-Fawares O, Hamadeneh L, Khawaldeh A PLoS One. 2024; 19(6):e0305636.

PMID: 38885232 PMC: 11182553. DOI: 10.1371/journal.pone.0305636.

Seminal plasma S100A8/A9 as a potential biomarker of genital tract inflammation.

Shen Q, Wang Y, Fang Y, Chen Y, He L, Zhang Y Asian J Androl. 2024; 26(5):464-471.

PMID: 38727211 PMC: 11449414. DOI: 10.4103/aja202389.

THC and sperm: Impact on fertilization capability, pre-implantation in vitro development and epigenetic modifications.

Kuzma-Hunt A, Sabry R, Davis O, Truong V, Khokhar J, Favetta L PLoS One. 2024; 19(3):e0298697.

PMID: 38536780 PMC: 10971525. DOI: 10.1371/journal.pone.0298697.

References

Tronchon V, Vialard F, El Sirkasi M, Dechaud H, ROLLET J, Albert M . Tumor necrosis factor-alpha -308 polymorphism in infertile men with altered sperm production or motility. Hum Reprod. 2008; 23(12):2858-66. DOI: 10.1093/humrep/den277. View

Petersen C, Froysa B, Soder O . Endotoxin and proinflammatory cytokines modulate Sertoli cell proliferation in vitro. J Reprod Immunol. 2004; 61(1):13-30. DOI: 10.1016/j.jri.2003.10.003. View

Comhaire F, Bosmans E, Ombelet W, Punjabi U, Schoonjans F . Cytokines in semen of normal men and of patients with andrological diseases. Am J Reprod Immunol. 1994; 31(2-3):99-103. DOI: 10.1111/j.1600-0897.1994.tb00853.x. View

Ochsendorf F . Infections in the male genital tract and reactive oxygen species. Hum Reprod Update. 1999; 5(5):399-420. DOI: 10.1093/humupd/5.5.399. View

OBryan M, Hedger M . Inflammatory networks in the control of spermatogenesis : chronic inflammation in an immunologically privileged tissue?. Adv Exp Med Biol. 2009; 636:92-114. DOI: 10.1007/978-0-387-09597-4_6. View

Hajeer A, Hutchinson I . Influence of TNFalpha gene polymorphisms on TNFalpha production and disease. Hum Immunol. 2001; 62(11):1191-9. DOI: 10.1016/s0198-8859(01)00322-6. View

Said T, Agarwal A, Falcone T, Sharma R, Bedaiwy M, Li L . Infliximab may reverse the toxic effects induced by tumor necrosis factor alpha in human spermatozoa: an in vitro model. Fertil Steril. 2005; 83(6):1665-73. DOI: 10.1016/j.fertnstert.2004.11.068. View

Shukla K, Chambial S, Dwivedi S, Misra S, Sharma P . Recent scenario of obesity and male fertility. Andrology. 2014; 2(6):809-18. DOI: 10.1111/andr.270. View

Dousset B, Hussenet F, Daudin M, Bujan L, Foliguet B, NABET P . Seminal cytokine concentrations (IL-1beta, IL-2, IL-6, sR IL-2, sR IL-6), semen parameters and blood hormonal status in male infertility. Hum Reprod. 1997; 12(7):1476-9. DOI: 10.1093/humrep/12.7.1476. View

10.

Khawar M, Mehmood R, Roohi N . MicroRNAs: Recent insights towards their role in male infertility and reproductive cancers. Bosn J Basic Med Sci. 2019; 19(1):31-42. PMC: 6387678. DOI: 10.17305/bjbms.2018.3477. View

11.

Huszar J, Payne C . MicroRNA 146 (Mir146) modulates spermatogonial differentiation by retinoic acid in mice. Biol Reprod. 2012; 88(1):15. PMC: 4434937. DOI: 10.1095/biolreprod.112.103747. View

12.

Abu-Halima M, Ayesh B, Hart M, Alles J, Fischer U, Hammadeh M . Differential expression of miR-23a/b-3p and its target genes in male patients with subfertility. Fertil Steril. 2019; 112(2):323-335.e2. DOI: 10.1016/j.fertnstert.2019.03.025. View

13.

Balasubramanian A, Thirumavalavan N, Pastuszak A . Evolving insights into the relationship between miR-23a/b-3p and target genes in subfertile patients. Fertil Steril. 2019; 112(2):241-242. PMC: 7333521. DOI: 10.1016/j.fertnstert.2019.04.036. View

14.

Lazzarini R, Olivieri F, Ferretti C, Mattioli-Belmonte M, Di Primio R, Orciani M . mRNAs and miRNAs profiling of mesenchymal stem cells derived from amniotic fluid and skin: the double face of the coin. Cell Tissue Res. 2013; 355(1):121-30. DOI: 10.1007/s00441-013-1725-4. View

15.

Finocchi F, Pelloni M, Balercia G, Pallotti F, Radicioni A, Lenzi A . Seminal plasma miRNAs in Klinefelter syndrome and in obstructive and non-obstructive azoospermia. Mol Biol Rep. 2020; 47(6):4373-4382. DOI: 10.1007/s11033-020-05552-x. View

16.

Seshadri S, Bates M, Vince G, Lewis Jones D . The role of cytokine expression in different subgroups of subfertile men. Am J Reprod Immunol. 2009; 62(5):275-82. DOI: 10.1111/j.1600-0897.2009.00736.x. View

17.

Agarwal A, Mulgund A, Sharma R, Sabanegh E . Mechanisms of oligozoospermia: an oxidative stress perspective. Syst Biol Reprod Med. 2014; 60(4):206-16. DOI: 10.3109/19396368.2014.918675. View

18.

Matthiesson K, McLachlan R, ODonnell L, Frydenberg M, Robertson D, Stanton P . The relative roles of follicle-stimulating hormone and luteinizing hormone in maintaining spermatogonial maturation and spermiation in normal men. J Clin Endocrinol Metab. 2006; 91(10):3962-9. DOI: 10.1210/jc.2006-1145. View

19.

Siciliano L, Tarantino P, Longobardi F, Rago V, De Stefano C, Carpino A . Impaired seminal antioxidant capacity in human semen with hyperviscosity or oligoasthenozoospermia. J Androl. 2001; 22(5):798-803. View

20.

Mauduit C, Besset V, Caussanel V, Benahmed M . Tumor necrosis factor alpha receptor p55 is under hormonal (follicle-stimulating hormone) control in testicular Sertoli cells. Biochem Biophys Res Commun. 1996; 224(3):631-7. DOI: 10.1006/bbrc.1996.1077. View