Lipopolysaccharide and lipotheicoic acid differentially modulate epididymal cytokine and chemokine profiles and sperm parameters in experimental acute epididymitis

Author(s)

Silva, Erick J. R. ^{[1, 2]} ; Ribeiro, Camilla M. ^[2] ; Mirim, Andre F. M. ^[2] ; Silva, Alan A. S. ^[1] ; Romano, Renata M. ^{[2, 3]} ; Hallak, Jorge ^{[4, 5, 6]} ; Avellar, Maria Christina W. ^[2]

Affiliation

^[1] Univ Estadual Paulista, Dept Pharmacol, Inst Biosci Botucatu, Botucatu, SP - Brazil

^[2] Univ Fed Sao Paulo, Escola Paulista Med, Sect Expt Endocrinol, Dept Pharmacol, BR-04044020 Sao Paulo, SP - Brazil

^[3] State Univ Centro Oeste, Dept Pharm, BR-85040080 Guarapuava, PR - Brazil

^[4] Sci & Innovat Ctr Androl, Androsci, BR-03178200 Sao Paulo, SP - Brazil

^[5] Univ Sao Paulo, Med Sch, Hosp Clin, Reprod Toxicol Unity, Dept Pathol, BR-01246903 Sao Paulo, SP - Brazil

^[6] Univ Sao Paulo, Med Sch, Hosp Clin, Div Urol, BR-01246903 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 8, JAN 8 2018.
• Web of Science Citations: 7

Abstract

Bacterial infections are the most prevalent etiological factors of epididymitis, a commonly diagnosed inflammatory disease in the investigation of male infertility factors. The influence of early pathogenic mechanisms at play during bacterial epididymitis on reproductive outcomes is little understood. We report here that experimental epididymitis induced in rats by Gram-negative (LPS) and Gram-positive (LTA) bacterial products resulted in differential patterns of acute inflammation in the cauda epididymis. LPS elicited a strong inflammatory reaction, as reflected by upregulation of levels of mRNA for seven inflammatory mediators (Il1b, Tnf, Il6, Ifng, Il10, Nos2 and Nfkbia), and tissue concentration of six cytokines/chemokines (IL1A, IL1B, IL6, IL10, CXCL2 and CCL2) within the first 24 h post-treatment. Conversely, LTA induced downregulation of one (Nfkbia) and upregulation of six (Il1b, Il6, Nos2, Il4 Il10 and Ptgs1) inflammatory gene transcripts, whereas increased the tissue concentration of three cytokines/chemokines (IL10, CXCL2 and CCL2). The stronger acute inflammatory response induced by LPS correlated with a reduction of epididymal sperm count and transit time that occurred at 1, 7, and 15 days post-treatment. Our study provides evidence that early epididymal inflammatory signaling events to bacterial activators of innate immunity may contribute to the detrimental effects of epididymitis upon male fertility. (AU)

• FAPESP's process: 15/08227-0 - A study on EPPIN as a drug target for male contraception: developing a new animal model to test the efficacy of male contraceptive drugs
• Grantee: Erick José Ramo da Silva
• Support Opportunities: Research Grants - Young Investigators Grants