Inflammation is among the core causatives of male infertility. Despite male infertility being a serious global issue, "bits and pieces" of its complex etiopathology still remain missing. During inflammation, levels of proinflammatory mediators in the male reproductive tract are greater than usual. According to epidemiological research, in numerous cases of male infertility, patients suffer from acute or chronic inflammation of the genitourinary tract which typically occurs without symptoms. Inflammatory responses in the male genital system are inextricably linked to oxidative stress (OS). OS is detrimental to male fertility parameters as it causes oxidative damage to reproductive cells and intracellular components. Multifarious male infertility causative factors pave the way for impairing male reproductive functions via the common mechanisms of OS and inflammation, both of which are interlinked pathophysiological processes, and the occurrence of any one of them induces the other. Both processes may be simultaneously found in the pathogenesis of male infertility. Thus, the present article aims to explain the role of inflammation and OS in male infertility in detail, as well as to show the mechanistic pathways that link causative factors of male reproductive tract inflammation, OS induction, and oxidant-sensitive cellular cascades leading to male infertility.

Department of Animal Morphology Physiology and Genetics Faculty of AgriSciences Mendel University in Brno Zemedelska 1 613 00 Brno Czech Republic

Department of Life Science and Bioinformatics Assam University Silchar 788011 India

Faculty of Dentistry MAHSA University Shah Alam 42610 Malaysia

Faculty of Medicine Bioscience and Nursing MAHSA University Shah Alam 42610 Malaysia

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Sengupta P., Dutta S., Krajewska-Kulak E. The Disappearing Sperms: Analysis of Reports Published Between 1980 and 2015. Am. J. Mens Health. 2017;11:1279–1304. doi: 10.1177/1557988316643383. PubMed DOI PMC

Sengupta P., Nwagha U., Dutta S., Krajewska-Kulak E., Izuka E. Evidence for decreasing sperm count in African population from 1965 to 2015. Afr. Health Sci. 2017;17:418–427. doi: 10.4314/ahs.v17i2.16. PubMed DOI PMC

Sengupta P., Dutta S., Tusimin M.B., İrez T., Krajewska-Kulak E. Sperm counts in Asian men: Reviewing the trend of past 50 years. Asian Pac. J. Reprod. 2018;7:87–92. doi: 10.4103/2305-0500.228018. DOI

Sengupta P. Reviewing reports of semen volume and male aging of last 33 years: From 1980 through 2013. Asian Pac. J. Reprod. 2015;4:242–246. doi: 10.1016/j.apjr.2015.06.010. DOI

Sengupta P., Borges E., Jr., Dutta S., Krajewska-Kulak E. Decline in sperm count in European men during the past 50 years. Hum. Exp. Toxicol. 2018;37:247–255. doi: 10.1177/0960327117703690. PubMed DOI

Bhattacharya K., Sengupta P., Dutta S., Karkada I.R. Obesity, systemic inflammation and male infertility. Chem. Biol. Lett. 2020;7:92–98.

Agarwal A., Leisegang K., Sengupta P. Pathology. Elsevier; Amsterdam, The Netherlands: 2020. Oxidative stress in pathologies of male reproductive disorders; pp. 15–27.

Dutta S., Sengupta P., Chhikara B.S. Reproductive inflammatory mediators and male infertility. Chem. Biol. Lett. 2020;7:73–74.

Leisegang K., Dutta S. Do lifestyle practices impede male fertility? Andrologia. 2021;53:e13595. doi: 10.1111/and.13595. PubMed DOI

Sabeti P., Pourmasumi S., Rahiminia T., Akyash F., Talebi A.R. Etiologies of sperm oxidative stress. Int. J. Reprod. Biomed. 2016;14:231–240. doi: 10.29252/ijrm.14.4.231. PubMed DOI PMC

Reuter S., Gupta S.C., Chaturvedi M.M., Aggarwal B.B. Oxidative stress, inflammation, and cancer: How are they linked? Free Radic. Biol. Med. 2010;49:1603–1616. doi: 10.1016/j.freeradbiomed.2010.09.006. PubMed DOI PMC

Agarwal A., Sengupta P. Male Infertility. Springer; Berlin/Heidelberg, Germany: 2020. Oxidative stress and its association with male infertility; pp. 57–68.

Azenabor A., Ekun A.O., Akinloye O. Impact of inflammation on male reproductive tract. J. Reprod. Infertil. 2015;16:123. PubMed PMC

Kumar N., Singh A.K. Trends of male factor infertility, an important cause of infertility: A review of literature. J. Hum. Reprod. Sci. 2015;8:191. doi: 10.4103/0974-1208.170370. PubMed DOI PMC

Selvam M.K.P., Sengupta P., Agarwal A. Genetics of Male Infertility. Springer; Berlin/Heidelberg, Germany: 2020. Sperm DNA fragmentation and male infertility; pp. 155–172.

Dutta S., Henkel R., Sengupta P., Agarwal A. Male Infertility. Springer; Berlin/Heidelberg, Germany: 2020. Physiological role of ROS in sperm function; pp. 337–345.

Thompson A., Agarwal A., du Plessis S.S. Physiological Role of Reactive Oxygen Species in Sperm Function: A Review. Antioxidants in Male Infertility: A Guide for Clinicians and Researchers. Springer Science and Business Media; New York, NY, USA: 2014. pp. 69–89.

Du Plessis S.S., Agarwal A., Halabi J., Tvrda E. Contemporary evidence on the physiological role of reactive oxygen species in human sperm function. J. Assist. Reprod. Genet. 2015;32:509–520. doi: 10.1007/s10815-014-0425-7. PubMed DOI PMC

Griveau J.F., Le Lannou D. Reactive oxygen species and human spermatozoa: Physiology and pathology. Int. J. Androl. 1997;20:61–69. doi: 10.1046/j.1365-2605.1997.00044.x. PubMed DOI

Balhorn R. A model for the structure of chromatin in mammalian sperm. J. Cell Biol. 1982;93:298–305. doi: 10.1083/jcb.93.2.298. PubMed DOI PMC

Saowaros W., Panyim S. The formation of disulfide bonds in human protamines during sperm maturation. Experientia. 1979;35:191–192. doi: 10.1007/BF01920608. PubMed DOI

Fujii J., Tsunoda S. Redox regulation of fertilisation and the spermatogenic process. Asian J. Androl. 2011;13:420–423. doi: 10.1038/aja.2011.10. PubMed DOI PMC

Hamada A., Sharma R., Du Plessis S.S., Willard B., Yadav S.P., Sabanegh E., Agarwal A. Two-dimensional differential in-gel electrophoresis–based proteomics of male gametes in relation to oxidative stress. Fertil. Steril. 2013;99:1216–1226.e2. doi: 10.1016/j.fertnstert.2012.11.046. PubMed DOI

Khosrowbeygi A., Zarghami N. Fatty acid composition of human spermatozoa and seminal plasma levels of oxidative stress biomarkers in subfertile males. Prostaglandins Leukot. Essent. 2007;77:117–121. doi: 10.1016/j.plefa.2007.08.003. PubMed DOI

Izuka E., Menuba I., Sengupta P., Dutta S., Nwagha U. Antioxidants, anti-inflammatory drugs and antibiotics in the treatment of reproductive tract infections and their association with male infertility. Chem. Biol. Lett. 2020;7:156–165.

Barati E., Nikzad H., Karimian M. Oxidative stress and male infertility: Current knowledge of pathophysiology and role of antioxidant therapy in disease management. Cell Mol. Life Sci. 2020;77:93–113. doi: 10.1007/s00018-019-03253-8. PubMed DOI PMC

Dutta S., Majzoub A., Agarwal A. Oxidative stress and sperm function: A systematic review on evaluation and management. Arab. J. Urol. 2019;17:87–97. doi: 10.1080/2090598X.2019.1599624. PubMed DOI PMC

Alahmar A.T., Calogero A.E., Sengupta P., Dutta S. Coenzyme Q10 improves sperm parameters, oxidative stress markers and sperm DNA fragmentation in infertile patients with idiopathic oligoasthenozoospermia. World J. Mens Health. 2021;39:346. doi: 10.5534/wjmh.190145. PubMed DOI PMC

Alahmar A.T., Sengupta P., Dutta S., Calogero A.E. Coenzyme Q10, oxidative stress markers, and sperm DNA damage in men with idiopathic oligoasthenoteratospermia. Clin. Exp. Reprod. Med. 2021;48:150. doi: 10.5653/cerm.2020.04084. PubMed DOI PMC

Cotran R.S. Robbins Pathological Basis of Disease. Elsevier Health Sciences; Philadelphia, PA, USA: 1999. Acute and chronic inflammation; pp. 50–88.

Anderson M.T., Staal F., Gitler C., Herzenberg L.A. Separation of oxidant-initiated and redox-regulated steps in the NF-kappa B signal transduction pathway. Proc. Natl. Acad. Sci. USA. 1994;91:11527–11531. doi: 10.1073/pnas.91.24.11527. PubMed DOI PMC

Flohé L., Brigelius-Flohé R., Saliou C., Traber M.G., Packer L. Redox regulation of NF-kappa B activation. Free Radic. Biol. Med. 1997;22:1115–1126. doi: 10.1016/S0891-5849(96)00501-1. PubMed DOI

Dohle G.R., Smit M., Weber R.F. Androgens and male fertility. World J. Urol. 2003;21:341–345. doi: 10.1007/s00345-003-0365-9. PubMed DOI

Garolla A., Pizzol D., Bertoldo A., Menegazzo M., Barzon L., Foresta C. Sperm viral infection and male infertility: Focus on HBV, HCV, HIV, HPV, HSV, HCMV, and AAV. J. Reprod. Immunol. 2013;100:20–29. doi: 10.1016/j.jri.2013.03.004. PubMed DOI

Jensen C.F.S., Østergren P., Dupree J.M., Ohl D.A., Sønksen J., Fode M. Varicocele and male infertility. Nat. Rev. Urol. 2017;14:523–533. doi: 10.1038/nrurol.2017.98. PubMed DOI

Laleman W., Claria J., Van der Merwe S., Moreau R., Trebicka J. Systemic inflammation and acute-on-chronic liver failure: Too much, not enough. Can. J. Gastroenterol. Hepatol. 2018;2018:1–11. doi: 10.1155/2018/1027152. PubMed DOI PMC

Sengupta P., Dutta S., D’Souza U., Alahmar A. Reproductive tract infection, inflammation and male infertility. Chem. Biol. Lett. 2020;7:75–84.

İrez T., Karkada I.R., Dutta S., Sengupta P. Obestatin in male reproduction and infertility. Chem. Biol. Lett. 2019;8:239.

Hammoud A.O., Gibson M., Peterson C.M., Meikle A.W., Carrell D.T. Impact of male obesity on infertility: A critical review of the current literature. Fertil. Steril. 2008;90:897–904. doi: 10.1016/j.fertnstert.2008.08.026. PubMed DOI

Irez T., Bicer S., Sahin S., Dutta S., Sengupta P. Cytokines and adipokines in the regulation of spermatogenesis and semen quality. Chem. Biol. Lett. 2020;7:131–139.

Dutta S., Biswas A., Sengupta P. Obesity, endocrine disruption and male infertility. Asian Pac. J. Reprod. 2019;8:195–201. doi: 10.4103/2305-0500.268133. DOI

Sengupta P., Bhattacharya K., Dutta S. Leptin and male reproduction. Asian Pac. J. Reprod. 2019;8:220–226. doi: 10.4103/2305-0500.268143. DOI

Davi G., Falco A. Oxidant stress, inflammation and atherogenesis. Lupus. 2005;14:760–764. doi: 10.1191/0961203305lu2216oa. PubMed DOI

Dandona P., Aljada A., Chaudhuri A., Mohanty P., Garg R. Metabolic syndrome: A comprehensive perspective based on interactions between obesity, diabetes, and inflammation. Circulation. 2005;111:1448–1454. doi: 10.1161/01.CIR.0000158483.13093.9D. PubMed DOI

Leisegang K., Sengupta P., Agarwal A., Henkel R. Obesity and male infertility: Mechanisms and management. Andrologia. 2021;53:e13617. doi: 10.1111/and.13617. PubMed DOI

Alahmar A.T., Calogero A.E., Singh R., Cannarella R., Sengupta P., Dutta S. Coenzyme Q10, oxidative stress, and male infertility: A review. Clin. Exp. Reprod. Med. 2021;48:97–104. doi: 10.5653/cerm.2020.04175. PubMed DOI PMC

Alahmar A.T., Sengupta P. Impact of Coenzyme Q10 and Selenium on Seminal Fluid Parameters and Antioxidant Status in Men with Idiopathic Infertility. Biol. Trace Elem. Res. 2021;199:1246–1252. doi: 10.1007/s12011-020-02251-3. PubMed DOI

Agarwal A., Sharma R.K., Desai N.R., Prabakaran S., Tavares A., Sabanegh E. Role of oxidative stress in pathogenesis of varicocele and infertility. Urology. 2009;73:461–469. doi: 10.1016/j.urology.2008.07.053. PubMed DOI

French D.B., Desai N.R., Agarwal A. Varicocele repair: Does it still have a role in infertility treatment? Curr. Opin. Obstet. Gynecol. 2008;20:269–274. doi: 10.1097/GCO.0b013e3282fcc00c. PubMed DOI

Pasqualotto F.F., Sundaram A., Sharma R.K., Borges E., Jr., Pasqualotto E.B., Agarwal A. Semen quality and oxidative stress scores in fertile and infertile patients with varicocele. Fertil. Steril. 2008;89:602–607. doi: 10.1016/j.fertnstert.2007.03.057. PubMed DOI

Ozbek E., Turkoz Y., Gokdeniz R., Davarci M., Ozugurlu F. Increased nitric oxide production in the spermatic vein of patients with varicocele. Eur. Urol. 2000;37:172–175. doi: 10.1159/000020135. PubMed DOI

Sultana T., Svechnikov K., Weber G., Söder O. Molecular cloning and expression of a functionally different alternative splice variant of prointerleukin-1alpha from the rat testis. Endocrinology. 2000;141:4413–4418. doi: 10.1210/endo.141.12.7824. PubMed DOI

Zeinali M., Hadian Amree A., Khorramdelazad H., Karami H., Abedinzadeh M. Inflammatory and anti-inflammatory cytokines in the seminal plasma of infertile men suffering from varicocele. Andrologia. 2017;49:1–4. doi: 10.1111/and.12685. PubMed DOI

Allen J.D., Gow A.J. Nitrite, NO and hypoxic vasodilation. Br. J. Pharmacol. 2009;158:1653–1654. doi: 10.1111/j.1476-5381.2009.00447.x. PubMed DOI PMC

Romeo C., Ientile R., Impellizzeri P., Turiaco N., Teletta M., Antonuccio P., Basile M., Gentile C. Preliminary report on nitric oxide-mediated oxidative damage in adolescent varicocele. Hum. Reprod. 2003;18:26–29. doi: 10.1093/humrep/deg004. PubMed DOI

Benoff S., Goodwin L.O., Millan C., Hurley I.R., Pergolizzi R.G., Marmar J.L. Deletions in L-type calcium channel alpha1 subunit testicular transcripts correlate with testicular cadmium and apoptosis in infertile men with varicoceles. Fertil. Steril. 2005;83:622–634. doi: 10.1016/j.fertnstert.2004.07.976. PubMed DOI

Coban S., Keles I., Biyik İ., Guzelsoy M., Turkoglu A.R., Ocak N. Does varicocele correction lead to normalization of preoperatively elevated mean platelet volume levels? Can. Urol. Assoc. J. 2015;9:E5–E9. doi: 10.5489/cuaj.2113. PubMed DOI PMC

Nazari A., Hassanshahi G., Khorramdelazad H. Elevated levels of epithelial neutrophil activating peptide-78 (ENA-78)(CXCL5) and Interleukin-1β is correlated with varicocele-caused infertility: A novel finding. Middle East Fertil. Soc. J. 2017;22:333–335. doi: 10.1016/j.mefs.2017.06.002. DOI

Hirik E., Suleyman B., Mammadov R., Yapanoglu T., Cimen F.K., Cetin N., Kurt N. Effect of anakinra, an interleukin one beta antagonist, on oxidative testicular damage induced in rats with ischemia reperfusion. Rev. Int. Androl. 2018;16:87–94. doi: 10.1016/j.androl.2017.03.001. PubMed DOI

Plante M., de Lamirande E., Gagnon C. Reactive oxygen species released by activated neutrophils, but not by deficient spermatozoa, are sufficient to affect normal sperm motility. Fertil. Steril. 1994;62:387–393. doi: 10.1016/S0015-0282(16)56895-2. PubMed DOI

Henkel R., Maass G., Jung A., Haidl G., Schill W.B., Schuppe H.C. Age-related changes in seminal polymorphonuclear elastase in men with asymptomatic inflammation of the genital tract. Asian J. Androl. 2007;9:299–304. doi: 10.1111/j.1745-7262.2007.00270.x. PubMed DOI

Wolff H. The biologic significance of white blood cells in semen. Fertil. Steril. 1995;63:1143–1157. doi: 10.1016/s0015-0282(16)57588-8. PubMed DOI

Mosser D.M., Edwards J.P. Exploring the full spectrum of macrophage activation. Nat. Rev. Immunol. 2008;8:958–969. doi: 10.1038/nri2448. PubMed DOI PMC

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;31:99–103. doi: 10.1111/j.1600-0897.1994.tb00853.x. PubMed DOI

Sandoval J.S., Raburn D., Muasher S. Leukocytospermia: Overview of diagnosis, implications, and management of a controversial finding. Middle East Fertil. Soc. J. 2013;18:129–134. doi: 10.1016/j.mefs.2013.02.004. DOI

Agarwal A., Saleh R.A., Bedaiwy M.A. Role of reactive oxygen species in the pathophysiology of human reproduction. Fertil. Steril. 2003;79:829–843. doi: 10.1016/S0015-0282(02)04948-8. PubMed DOI

Aziz N., Agarwal A., Lewis-Jones I., Sharma R.K., Thomas A.J., Jr. Novel associations between specific sperm morphological defects and leukocytospermia. Fertil. Steril. 2004;82:621–627. doi: 10.1016/j.fertnstert.2004.02.112. PubMed DOI

Saleh R.A., Agarwal A., Kandirali E., Sharma R.K., Thomas A.J., Nada E.A., Evenson D.P., Alvarez J.G. Leukocytospermia is associated with increased reactive oxygen species production by human spermatozoa. Fertil. Steril. 2002;78:1215–1224. doi: 10.1016/S0015-0282(02)04237-1. PubMed DOI

Hagan S., Khurana N., Chandra S., Abdel-Mageed A.B., Mondal D., Hellstrom W.J., Sikka S.C. Differential expression of novel biomarkers (TLR-2, TLR-4, COX-2, and Nrf-2) of inflammation and oxidative stress in semen of leukocytospermia patients. Andrology. 2015;3:848–855. doi: 10.1111/andr.12074. PubMed DOI

Mazzoli S., Cai T., Addonisio P., Bechi A., Mondaini N., Bartoletti R. Chlamydia trachomatis infection is related to poor semen quality in young prostatitis patients. Eur. Urol. 2010;57:708–714. doi: 10.1016/j.eururo.2009.05.015. PubMed DOI

Ouzounova-Raykova V., Rangelov S., Ouzounova I., Mitov I. Detection of Chlamydia trachomatis, Ureaplasma urealyticum and Mycoplasma hominis in infertile Bulgarian men with multiplex real-time polymerase chain reaction. Apmis. 2015;123:586–588. doi: 10.1111/apm.12391. PubMed DOI

Galdiero F., Sommese L., Gorga F., Galdiero E., Rizzo A., Ajello M. Toxic effect on human spermatozoa by Chlamydia trachomatis purified lipopolysaccharide. FEMS Microbiol. Lett. 1994;115:197–200. doi: 10.1111/j.1574-6968.1994.tb06637.x. PubMed DOI

Nunez-Calonge R., Caballero P., Redondo C., Baquero F., Martinez-Ferrer M., Meseguer M. Ureaplasma urealyticum reduces motility and induces membrane alterations in human spermatozoa. Hum. Reprod. 1998;13:2756–2761. doi: 10.1093/humrep/13.10.2756. PubMed DOI

Jarecki-Black J., Lushbaugh W., Golosov L., Glassman A. Trichomonas vaginalis: Preliminary characterization of a sperm motility inhibiting factor. Ann. Clin. Lab. Sci. 1988;18:484–489. PubMed

Alshahrani S., McGill J., Agarwal A. Prostatitis and male infertility. J. Reprod. Immunol. 2013;100:30–36. doi: 10.1016/j.jri.2013.05.004. PubMed DOI

Sanocka D., Kurpisz M. Reactive oxygen species and sperm cells. Reprod. Biol. Endocrinol. 2004;2:12. doi: 10.1186/1477-7827-2-12. PubMed DOI PMC

Martínez P., Proverbio F., Camejo M.I. Sperm lipid peroxidation and pro-inflammatory cytokines. Asian J. Androl. 2007;9:102–107. doi: 10.1111/j.1745-7262.2007.00238.x. PubMed DOI

Tremellen K. Oxidative stress and male infertility—A clinical perspective. Hum. Reprod. Update. 2008;14:243–258. doi: 10.1093/humupd/dmn004. PubMed DOI

Sharma A. Male infertility; evidences, risk factors, causes, diagnosis and management in human. Ann. Clin. Lab. Res. 2017;5:188. doi: 10.21767/2386-5180.1000188. DOI

Schuppe H.C., Meinhardt A., Allam J., Bergmann M., Weidner W., Haidl G. Chronic orchitis: A neglected cause of male infertility? Andrologia. 2008;40:84–91. doi: 10.1111/j.1439-0272.2008.00837.x. PubMed DOI

Lipsky B.A., Byren I., Hoey C.T. Treatment of bacterial prostatitis. Clin. Infect. Dis. 2010;50:1641–1652. doi: 10.1086/652861. PubMed DOI

Krupp K., Madhivanan P. Antibiotic resistance in prevalent bacterial and protozoan sexually transmitted infections. Indian J. Sex. Transm. Dis. AIDS. 2015;36:3. doi: 10.4103/0253-7184.156680. PubMed DOI PMC

Magri V., Trinchieri A., Pozzi G., Restelli A., Garlaschi M.C., Torresani E., Zirpoli P., Marras E., Perletti G. Efficacy of repeated cycles of combination therapy for the eradication of infecting organisms in chronic bacterial prostatitis. Int. J. Antimicrob. Agents. 2007;29:549–556. doi: 10.1016/j.ijantimicag.2006.09.027. PubMed DOI

Oliphant C.M., Green G. Quinolones: A comprehensive review. Am. Fam. Physician. 2002;65:455. PubMed

Costello L., Feng P., Milon B., Tan M., Franklin R. Role of zinc in the pathogenesis and treatment of prostate cancer: Critical issues to resolve. Prostate Cancer Prostatic Dis. 2004;7:111–117. doi: 10.1038/sj.pcan.4500712. PubMed DOI PMC

Krause W., Bohring C. Male infertility and genital chlamydial infection: Victim or perpetrator? Andrologia. 2003;35:209–216. doi: 10.1046/j.1439-0272.2003.00561.x. PubMed DOI

Workowski K.A., Berman S.M. Sexually Transmitted Diseases Treatment Guidelines. Volume 59 Department of Health and Human Services; Washington, DC, USA: 2010.

Raz R., Colodner R., Kunin C.M. Who are you—Staphylococcus saprophyticus? Clin. Infect. Dis. 2005;40:896–898. doi: 10.1086/428353. PubMed DOI

Dutta S., Sengupta P., Izuka E., Menuba I., Jegasothy R., Nwagha U. Staphylococcal infections and infertility: Mechanisms and management. Mol. Cell Biochem. 2020;474:57–72. doi: 10.1007/s11010-020-03833-4. PubMed DOI

Garolla A., Torino M., Sartini B., Cosci I., Patassini C., Carraro U., Foresta C. Seminal and molecular evidence that sauna exposure affects human spermatogenesis. Hum. Reprod. 2013;28:877–885. doi: 10.1093/humrep/det020. PubMed DOI

Kehl S., Weigel M., Müller D., Gentili M., Hornemann A., Sütterlin M. HIV-infection and modern antiretroviral therapy impair sperm quality. Arch. Gynecol. Obstet. 2011;284:229–233. doi: 10.1007/s00404-011-1898-6. PubMed DOI

Pavili L., Daudin M., Moinard N., Walschaerts M., Cuzin L., Massip P., Pasquier C., Bujan L. Decrease of mitochondrial DNA level in sperm from patients infected with human immunodeficiency virus-1 linked to nucleoside analogue reverse transcriptase inhibitors. Fertil. Steril. 2010;94:2151–2156. doi: 10.1016/j.fertnstert.2009.12.080. PubMed DOI

Frapsauce C., Grabar S., Leruez-Ville M., Launay O., Sogni P., Gayet V., Viard J., De Almeida M., Jouannet P., Dulioust E. Impaired sperm motility in HIV-infected men: An unexpected adverse effect of efavirenz? Hum. Reprod. 2015;30:1797–1806. doi: 10.1093/humrep/dev141. PubMed DOI

La Vignera S., Vicari E., Condorelli R., d’Agata R., Calogero A. Male accessory gland infection and sperm parameters. Int. J. Androl. 2011;34:e330–e347. doi: 10.1111/j.1365-2605.2011.01200.x. PubMed DOI

Zhou Y.H., Ma H.X., Shi X.X., Liu Y. Ureaplasma spp. in male infertility and its relationship with semen quality and seminal plasma components. J. Microbiol. Immunol. Infect. 2018;51:778–783. doi: 10.1016/j.jmii.2016.09.004. PubMed DOI

Kang X., Xie Q., Zhou X., Li F., Huang J., Liu D., Huang T. Effects of hepatitis B virus S protein exposure on sperm membrane integrity and functions. PLoS ONE. 2012;7:e33471. doi: 10.1371/journal.pone.0033471. PubMed DOI PMC

Qian L., Li Q., Li H. Effect of hepatitis B virus infection on sperm quality and oxidative stress state of the semen of infertile males. Am. J. Reprod. Immunol. 2016;76:183–185. doi: 10.1111/aji.12537. PubMed DOI

Sacks-Davis R., McBryde E., Grebely J., Hellard M., Vickerman P. Many hepatitis C reinfections that spontaneously clear may be undetected: Markov-chain Monte Carlo analysis of observational study data. J. R. Soc. Interface. 2015;12:20141197. doi: 10.1098/rsif.2014.1197. PubMed DOI PMC

Benova L., Mohamoud Y.A., Calvert C., Abu-Raddad L.J. Vertical transmission of hepatitis C virus: Systematic review and meta-analysis. Clin. Infect. Dis. 2014;59:765–773. doi: 10.1093/cid/ciu447. PubMed DOI PMC

Machida K., Cheng K.T.-H., Lai C.-K., Jeng K.-S., Sung V.M.-H., Lai M.M. Hepatitis C virus triggers mitochondrial permeability transition with production of reactive oxygen species, leading to DNA damage and STAT3 activation. J. Virol. 2006;80:7199–7207. doi: 10.1128/JVI.00321-06. PubMed DOI PMC

La Vignera S., Condorelli R., Vicari E., D’agata R., Calogero A. High frequency of sexual dysfunction in patients with male accessory gland infections. Andrologia. 2012;44:438–446. doi: 10.1111/j.1439-0272.2011.01202.x. PubMed DOI

Sengupta P., Leisegang K., Agarwal A. The impact of COVID-19 on the male reproductive tract and fertility: A systematic review. Arab. J. Urol. 2021;19:423–436. doi: 10.1080/2090598X.2021.1955554. PubMed DOI PMC

Xu J., Qi L., Chi X., Yang J., Wei X., Gong E., Peh S., Gu J. Orchitis: A complication of severe acute respiratory syndrome (SARS) Biol. Reprod. 2006;74:410–416. doi: 10.1095/biolreprod.105.044776. PubMed DOI PMC

Montano L., Donato F., Bianco P.M., Lettieri G., Guglielmino A., Motta O., Bonapace I.M., Piscopo M. Air Pollution and COVID-19: A Possible Dangerous Synergy for Male Fertility. Int. J. Environ. Res. Public Health. 2021;18:1–21.:6846. doi: 10.3390/ijerph18136846. PubMed DOI PMC

Itoh M., Hiramine C., Tokunaga Y., Mukasa A., Hojo K. A new murine model of autoimmune orchitis induced by immunization with viable syngeneic testicular germ cells alone. II. Immunohistochemical findings of fully-developed inflammatory lesion. Autoimmunity. 1991;10:89–97. doi: 10.3109/08916939109004812. PubMed DOI

Bhattacharya K., Mukhopadhyay L.D., Goswami R., Dutta S., Sengupta P., Irez T., Hamid H.A., Syamal A.K. SARS-CoV-2 infection and human semen: Possible modes of contamination and transmission. Middle East Fertil. Soc. J. 2021;26:18. doi: 10.1186/s43043-021-00063-6. PubMed DOI PMC

Dutta S., Sengupta P. SARS-CoV-2 and Male Infertility: Possible Multifaceted Pathology. Reprod. Sci. 2021;28:23–26. doi: 10.1007/s43032-020-00261-z. PubMed DOI PMC

Dutta S., Sengupta P. SARS-CoV-2 infection, oxidative stress and male reproductive hormones: Can testicular-adrenal crosstalk be ruled-out? J. Basic Clin. Physiol. Pharmacol. 2020;31:1–4. doi: 10.1515/jbcpp-2020-0205. PubMed DOI

Bouayed J., Rammal H., Soulimani R. Oxidative stress and anxiety: Relationship and cellular pathways. Oxid. Med. Cell. Longev. 2009;2:63–67. doi: 10.4161/oxim.2.2.7944. PubMed DOI PMC

Sengupta P., Dutta S. Does SARS-CoV-2 infection cause sperm DNA fragmentation? Possible link with oxidative stress. Eur. J. Contracept. Reprod. Health Care. 2020;25:405–406. doi: 10.1080/13625187.2020.1787376. PubMed DOI

DePalma A.F., Rothman R.H., Lewinnek G.E., Canale S.T. Anterior interbody fusion for severe cervical disc degeneration. Surg. Gynecol. Obstet. 1972;134:755–758. PubMed

Purvis K., Christiansen E. Infection in the male reproductive tract. Impact, diagnosis and treatment in relation to male infertility. Int. J. Androl. 1993;16:1–13. doi: 10.1111/j.1365-2605.1993.tb01146.x. PubMed DOI

Comhaire F.H., Mahmoud A.M., Depuydt C.E., Zalata A.A., Christophe A.B. Mechanisms and effects of male genital tract infection on sperm quality and fertilizing potential: The andrologist’s viewpoint. Hum. Reprod. Update. 1999;5:393–398. doi: 10.1093/humupd/5.5.393. PubMed DOI

Hales D.B., Diemer T., Hales K.H. Role of cytokines in testicular function. Endocrine. 1999;10:201–217. doi: 10.1007/BF02738619. PubMed DOI

Söder O., Sultana T., Jonsson C., Wahlgren A., Petersen C., Holst M. The interleukin-1 system in the testis. Andrologia. 2000;32:52–55. PubMed

Diemer T., Hales D.B., Weidner W. Immune-endocrine interactions and Leydig cell function: The role of cytokines. Andrologia. 2003;35:55–63. doi: 10.1046/j.1439-0272.2003.00537.x. PubMed DOI

Maegawa M., Kamada M., Irahara M., Yamamoto S., Yoshikawa S., Kasai Y., Ohmoto Y., Gima H., Thaler C.J., Aono T. A repertoire of cytokines in human seminal plasma. J. Reprod. Immunol. 2002;54:33–42. doi: 10.1016/S0165-0378(01)00063-8. PubMed DOI

Cudicini C., Lejeune H., Gomez E., Bosmans E., Ballet F., Saez J., Jégou B. Human Leydig cells and Sertoli cells are producers of interleukins-1 and -6. J. Clin. Endocrinol. Metab. 1997;82:1426–1433. doi: 10.1210/jc.82.5.1426. PubMed DOI

Turvey S.E., Broide D.H. Innate immunity. J. Allergy Clin. Immunol. 2010;125:S24–S32. doi: 10.1016/j.jaci.2009.07.016. PubMed DOI PMC

Keck C., Gerber-Schäfer C., Clad A., Wilhelm C., Breckwoldt M. Seminal tract infections: Impact on male fertility and treatment options. Hum. Reprod. Update. 1998;4:891–903. doi: 10.1093/humupd/4.6.891. PubMed DOI

Potts J.M., Sharma R., Pasqualotto F., Nelson D., Hall G., Agarwal A. Association of ureaplasma urealyticum with abnormal reactive oxygen species levels and absence of leukocytospermia. J. Urol. 2000;163:1775–1778. doi: 10.1016/S0022-5347(05)67540-4. PubMed DOI

Agarwal A., Majzoub A., Baskaran S., Selvam M.K.P., Cho C.L., Henkel R., Finelli R., Leisegang K., Sengupta P., Barbarosie C. Sperm DNA fragmentation: A new guideline for clinicians. World J. Mens Health. 2020;38:412. doi: 10.5534/wjmh.200128. PubMed DOI PMC

Agarwal A., Sekhon L.H. The role of antioxidant therapy in the treatment of male infertility. Hum. Fertil. 2010;13:217–225. doi: 10.3109/14647273.2010.532279. PubMed DOI

Valko M., Leibfritz D., Moncol J., Cronin M.T., Mazur M., Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell Biol. 2007;39:44–84. doi: 10.1016/j.biocel.2006.07.001. PubMed DOI

Agarwal A., Prabakaran S.A. Oxidative stress and antioxidants in male infertility: A difficult balance. Int. J. Reprod. Med. 2005;3:1–8.

Henkel R., Sandhu I.S., Agarwal A. The excessive use of antioxidant therapy: A possible cause of male infertility? Andrologia. 2019;51:e13162. doi: 10.1111/and.13162. PubMed DOI

Darbandi M., Darbandi S., Agarwal A., Baskaran S., Sengupta P., Dutta S., Mokarram P., Saliminejad K., Sadeghi M.R. Oxidative stress-induced alterations in seminal plasma antioxidants: Is there any association with keap1 gene methylation in human spermatozoa? Andrologia. 2019;51:e13159. doi: 10.1111/and.13159. PubMed DOI

Yu B., Huang Z. Variations in Antioxidant Genes and Male Infertility. BioMed Res. Int. 2015;2015:513196. doi: 10.1155/2015/513196. PubMed DOI PMC

Carrell D.T., Aston K.I. The search for SNPs, CNVs, and epigenetic variants associated with the complex disease of male infertility. Syst. Biol. Reprod. Med. 2011;57:17–26. doi: 10.3109/19396368.2010.521615. PubMed DOI

Kemal Duru N., Morshedi M., Oehninger S. Effects of hydrogen peroxide on DNA and plasma membrane integrity of human spermatozoa. Fertil. Steril. 2000;74:1200–1207. doi: 10.1016/S0015-0282(00)01591-0. PubMed DOI

Naz R.K., Evans L. Presence and modulation of interleukin-12 in seminal plasma of fertile and infertile men. J. Androl. 1998;19:302–307. PubMed

Gruschwitz M.S., Brezinschek R., Brezinschek H.P. Cytokine levels in the seminal plasma of infertile males. J. Androl. 1996;17:158–163. PubMed

Agarwal A., Parekh N., Selvam M.K.P., Henkel R., Shah R., Homa S.T., Ramasamy R., Ko E., Tremellen K., Esteves S. Male oxidative stress infertility (MOSI): Proposed terminology and clinical practice guidelines for management of idiopathic male infertility. World J. Mens Health. 2019;37:296. doi: 10.5534/wjmh.190055. PubMed DOI PMC

Aitken R.J., Clarkson J.S. Cellular basis of defective sperm function and its association with the genesis of reactive oxygen species by human spermatozoa. Reproduction. 1987;81:459–469. doi: 10.1530/jrf.0.0810459. PubMed DOI

Sharma R.K., Pasqualotto F.F., Nelson D.R., Agarwal A. Relationship between seminal white blood cell counts and oxidative stress in men treated at an infertility clinic. J. Androl. 2001;22:575–583. PubMed

Koppers A.J., Garg M.L., Aitken R.J. Stimulation of mitochondrial reactive oxygen species production by unesterified, unsaturated fatty acids in defective human spermatozoa. Free Radic. Biol. Med. 2010;48:112–119. doi: 10.1016/j.freeradbiomed.2009.10.033. PubMed DOI

Iwasaki A., Gagnon C. Formation of reactive oxygen species in spermatozoa of infertile patients. Fertil. Steril. 1992;57:409–416. doi: 10.1016/S0015-0282(16)54855-9. PubMed DOI

Williams A., Ford W. Functional significance of the pentose phosphate pathway and glutathione reductase in the antioxidant defenses of human sperm. Biol. Reprod. 2004;71:1309–1316. doi: 10.1095/biolreprod.104.028407. PubMed DOI

Bui A., Sharma R., Henkel R., Agarwal A. Reactive oxygen species impact on sperm DNA and its role in male infertility. Andrologia. 2018;50:e13012. doi: 10.1111/and.13012. PubMed DOI

Sengupta P., Durairajanayagam D., Agarwal A. Male Infertility. Springer; Berlin/Heidelberg, Germany: 2020. Fuel/energy sources of spermatozoa; pp. 323–335.

Aitken J., Fisher H. Reactive oxygen species generation and human spermatozoa: The balance of benefit and risk. Bioessays. 1994;16:259–267. doi: 10.1002/bies.950160409. PubMed DOI

Tavilani H., Goodarzi M.T., Vaisi-Raygani A., Salimi S., Hassanzadeh T. Activity of antioxidant enzymes in seminal plasma and their relationship with lipid peroxidation of spermatozoa. Int. Braz. J. Urol. 2008;34:485–491. doi: 10.1590/S1677-55382008000400011. PubMed DOI

Jones R., Mann T., Sherins R. Peroxidative breakdown of phospholipids in human spermatozoa, spermicidal properties of fatty acid peroxides, and protective action of seminal plasma. Fertil. Steril. 1979;31:531–537. doi: 10.1016/S0015-0282(16)43999-3. PubMed DOI

Aitken R., Harkiss D., Buckingham D. Analysis of lipid peroxidation mechanisms in human spermatozoa. Mol. Reprod. Dev. 1993;35:302–315. doi: 10.1002/mrd.1080350313. PubMed DOI

Sengupta P., Arafa M., Elbardisi H. Molecular Signaling in Spermatogenesis and Male Infertility. CRC Press; Boca Raton, FL, USA: 2019. Hormonal regulation of spermatogenesis; pp. 41–49.

Wells D., Bermudez M., Steuerwald N., Thornhill A., Walker D., Malter H., Delhanty J., Cohen J. Expression of genes regulating chromosome segregation, the cell cycle and apoptosis during human preimplantation development. Hum. Reprod. 2005;20:1339–1348. doi: 10.1093/humrep/deh778. PubMed DOI

Sakkas D., Alvarez J.G. Sperm DNA fragmentation: Mechanisms of origin, impact on reproductive outcome, and analysis. Fertil. Steril. 2010;93:1027–1036. doi: 10.1016/j.fertnstert.2009.10.046. PubMed DOI

Tesarik J., Greco E., Mendoza C. Late, but not early, paternal effect on human embryo development is related to sperm DNA fragmentation. Hum. Reprod. 2004;19:611–615. doi: 10.1093/humrep/deh127. PubMed DOI

Tesařík J., Kopečný V., Plachot M., Mandelbaum J. Activation of nucleolar and extranucleolar RNA synthesis and changes in the ribosomal content of human embryos developing in vitro. Reproduction. 1986;78:463–470. doi: 10.1530/jrf.0.0780463. PubMed DOI

Kuroda S., Takeshima T., Takeshima K., Usui K., Yasuda K., Sanjo H., Kawahara T., Uemura H., Murase M., Yumura Y. Early and late paternal effects of reactive oxygen species in semen on embryo development after intracytoplasmic sperm injection. Syst. Biol. Reprod. Med. 2020;66:122–128. doi: 10.1080/19396368.2020.1720865. PubMed DOI

Guerin P., Matillon C., Bleau G., Levy R., Menezo Y. Impact of sperm DNA fragmentation on ART outcome. Gynecol. Obstet. Fertil. Senol. 2005;33:665–668. doi: 10.1016/j.gyobfe.2005.07.015. PubMed DOI

Simon L., Zini A., Dyachenko A., Ciampi A., Carrell D.T. A systematic review and meta-analysis to determine the effect of sperm DNA damage on in vitro fertilization and intracytoplasmic sperm injection outcome. Asian J. Androl. 2017;19:80. doi: 10.4103/1008-682X.182822. PubMed DOI PMC

Zhao J., Zhang Q., Wang Y., Li Y. Whether sperm deoxyribonucleic acid fragmentation has an effect on pregnancy and miscarriage after in vitro fertilization/intracytoplasmic sperm injection: A systematic review and meta-analysis. Fertil. Steril. 2014;102:998–1005.e8. doi: 10.1016/j.fertnstert.2014.06.033. PubMed DOI

Trevelyan S.J., Brewster J.L., Burgess A.E., Crowther J.M., Cadell A.L., Parker B.L., Croucher D.R., Dobson R.C., Murphy J.M., Mace P.D. Structure-based mechanism of preferential complex formation by apoptosis signal–regulating kinases. Sci. Signal. 2020;13:1–26. doi: 10.1126/scisignal.aay6318. PubMed DOI

Shukla K.K., Mahdi A.A., Rajender S. Apoptosis, spermatogenesis and male infertility. Front. Biosci. 2012;4:746–754. doi: 10.2741/e415. PubMed DOI

Latchoumycandane C., Vaithinathan S., D’Cruz S., Mathur P.P. Male Infertility. Springer; Berlin/Heidelberg, Germany: 2020. Apoptosis and male infertility; pp. 479–486.

O’Bryan M., Schlatt S., Gerdprasert O., Phillips D.J., de Kretser D.M., Hedger M.P. Inducible nitric oxide synthase in the rat testis: Evidence for potential roles in both normal function and inflammation-mediated infertility. Biol. Reprod. 2000;63:1285–1293. doi: 10.1095/biolreprod63.5.1285. PubMed DOI

Gow R.M., O’Bryan M., Canny B., Ooi G.T., Hedger M. Differential effects of dexamethasone treatment on lipopolysaccharide-induced testicular inflammation and reproductive hormone inhibition in adult rats. J. Endocrinol. 2001;168:193–202. doi: 10.1677/joe.0.1680193. PubMed DOI

Ogilvie K.M., Held Hales K., Roberts M.E., Buchanan Hales D., Rivier C. The inhibitory effect of intracerebroventricularly injected interleukin 1β on testosterone secretion in the rat: Role of steroidogenic acute regulatory protein. Biol. Reprod. 1999;60:527–533. doi: 10.1095/biolreprod60.2.527. PubMed DOI

Dutta S., Sengupta P., Hassan M.F., Biswas A. Role of toll-like receptors in the reproductive tract inflammation and male infertility. Chem. Biol. Lett. 2020;7:113–123.

Kawai T., Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity. 2011;34:637–650. doi: 10.1016/j.immuni.2011.05.006. PubMed DOI

Riccioli A., Starace D., Galli R., Fuso A., Scarpa S., Palombi F., De Cesaris P., Ziparo E., Filippini A. Sertoli cells initiate testicular innate immune responses through TLR activation. J. Immunol. 2006;177:7122–7130. doi: 10.4049/jimmunol.177.10.7122. PubMed DOI

Bhushan S., Tchatalbachev S., Klug J., Fijak M., Pineau C., Chakraborty T., Meinhardt A. Uropathogenic Escherichia coli block MyD88-dependent and activate MyD88-independent signaling pathways in rat testicular cells. J. Immunol. 2008;180:5537–5547. doi: 10.4049/jimmunol.180.8.5537. PubMed DOI

Wu H., Wang H., Xiong W., Chen S., Tang H., Han D. Expression patterns and functions of toll-like receptors in mouse sertoli cells. Endocrinology. 2008;149:4402–4412. doi: 10.1210/en.2007-1776. PubMed DOI

Winnall W.R., Muir J.A., Hedger M.P. Differential responses of epithelial Sertoli cells of the rat testis to Toll-like receptor 2 and 4 ligands: Implications for studies of testicular inflammation using bacterial lipopolysaccharides. Innate Immun. 2011;17:123–136. doi: 10.1177/1753425909354764. PubMed DOI

Lui W.-Y., Wong C.-H., Mruk D.D., Cheng C.Y. TGF-β3 regulates the blood-testis barrier dynamics via the p38 mitogen activated protein (MAP) kinase pathway: An in vivo study. Endocrinology. 2003;144:1139–1142. doi: 10.1210/en.2002-0211. PubMed DOI

Okuma Y., Saito K., O’connor A., Phillips D.J., de Kretser D.M., Hedger M.P. Reciprocal regulation of activin A and inhibin B by interleukin-1 (IL-1) and follicle-stimulating hormone (FSH) in rat Sertoli cells in vitro. J. Endocrinol. 2005;185:99–110. doi: 10.1677/joe.1.06053. PubMed DOI

Hedger M.P. Toll-like receptors and signalling in spermatogenesis and testicular responses to inflammation—A perspective. J. Reprod. Immunol. 2011;88:130–141. doi: 10.1016/j.jri.2011.01.010. PubMed DOI PMC

O’Bryan M.K., Hedger M.P. Molecular Mechanisms in Spermatogenesis. Springer; Berlin/Heidelberg, Germany: 2009. Inflammatory networks in the control of spermatogenesis; pp. 92–114.

Shang T., Zhang X., Wang T., Sun B., Deng T., Han D. Toll-like receptor-initiated testicular innate immune responses in mouse Leydig cells. Endocrinology. 2011;152:2827–2836. doi: 10.1210/en.2011-0031. PubMed DOI

Samir M.S., Glister C., Mattar D., Laird M., Knight P.G. Follicular expression of pro-inflammatory cytokines tumour necrosis factor-α (TNFα), interleukin 6 (IL6) and their receptors in cattle: TNFα, IL6 and macrophages suppress thecal androgen production in vitro. Reproduction. 2017;154:35–49. doi: 10.1530/REP-17-0053. PubMed DOI

Ding D.-C., Liu H.-W., Chu T.-Y. Interleukin-6 from ovarian mesenchymal stem cells promotes proliferation, sphere and colony formation and tumorigenesis of an ovarian cancer cell line SKOV3. J. Cancer. 2016;7:1815. doi: 10.7150/jca.16116. PubMed DOI PMC

Frungieri M.B., Calandra R.S., Lustig L., Meineke V., Köhn F.M., Vogt H.-J., Mayerhofer A. Number, distribution pattern, and identification of macrophages in the testes of infertile men. Fertil. Steril. 2002;78:298–306. doi: 10.1016/S0015-0282(02)03206-5. PubMed DOI

Fehervari Z. Testicular macrophage origin. Nat. Immunol. 2017;18:1067. doi: 10.1038/ni.3846. PubMed DOI

Aslani F., Schuppe H.-C., Guazzone V.A., Bhushan S., Wahle E., Lochnit G., Lustig L., Meinhardt A., Fijak M. Targeting high mobility group box protein 1 ameliorates testicular inflammation in experimental autoimmune orchitis. Hum. Reprod. 2015;30:417–431. doi: 10.1093/humrep/deu320. PubMed DOI

Allen J.A., Diemer T., Janus P., Hales K.H., Hales D.B. Bacterial endotoxin lipopolysaccharide and reactive oxygen species inhibit Leydig cell steroidogenesis via perturbation of mitochondria. Endocrine. 2004;25:265–275. doi: 10.1385/ENDO:25:3:265. PubMed DOI

Choi Y.Y., Kim M.H., Han J.M., Hong J., Lee T.-H., Kim S.-H., Yang W.M. The anti-inflammatory potential of Cortex Phellodendron in vivo and in vitro: Down-regulation of NO and iNOS through suppression of NF-κB and MAPK activation. Int. Immunopharmacol. 2014;19:214–220. doi: 10.1016/j.intimp.2014.01.020. PubMed DOI

Kim S.Y., Jeong J.-M., Kim S.J., Seo W., Kim M.-H., Choi W.-M., Yoo W., Lee J.-H., Shim Y.-R., Yi H.-S. Pro-inflammatory hepatic macrophages generate ROS through NADPH oxidase 2 via endocytosis of monomeric TLR4–MD2 complex. Nat. Commun. 2017;8:1–15. doi: 10.1038/s41467-017-02325-2. PubMed DOI PMC

Zhou R., Yazdi A.S., Menu P., Tschopp J. A role for mitochondria in NLRP3 inflammasome activation. Nature. 2011;469:221–225. doi: 10.1038/nature09663. PubMed DOI

Shimada K., Crother T.R., Karlin J., Dagvadorj J., Chiba N., Chen S., Ramanujan V.K., Wolf A.J., Vergnes L., Ojcius D.M., et al. Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity. 2012;36:401–414. doi: 10.1016/j.immuni.2012.01.009. PubMed DOI PMC

Zhou R., Tardivel A., Thorens B., Choi I., Tschopp J. Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nat. Immunol. 2010;11:136–140. doi: 10.1038/ni.1831. PubMed DOI

Schroder K., Tschopp J. The inflammasomes. Cell. 2010;140:821–832. doi: 10.1016/j.cell.2010.01.040. PubMed DOI

Aguilera-Aguirre L., Bacsi A., Radak Z., Hazra T.K., Mitra S., Sur S., Brasier A.R., Ba X., Boldogh I. Innate inflammation induced by the 8-oxoguanine DNA glycosylase-1-KRAS-NF-κB pathway. J. Immunol. 2014;193:4643–4653. doi: 10.4049/jimmunol.1401625. PubMed DOI PMC

Iyer S.S., Accardi C.J., Ziegler T.R., Blanco R.A., Ritzenthaler J.D., Rojas M., Roman J., Jones D.P. Cysteine redox potential determines pro-inflammatory IL-1beta levels. PLoS ONE. 2009;4:e5017. doi: 10.1371/journal.pone.0005017. PubMed DOI PMC

Go Y.M., Jones D.P. Intracellular proatherogenic events and cell adhesion modulated by extracellular thiol/disulfide redox state. Circulation. 2005;111:2973–2980. doi: 10.1161/CIRCULATIONAHA.104.515155. PubMed DOI

Reactive Nitrogen Species and Male Reproduction: Physiological and Pathological Aspects

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