leptin and Epididymitis

Epididymitis, one of the most common urological disease, is a significant cause of male infertility. Leptin is capable of modulating both reproduction and immune response. We analyzed the serum and seminal plasma levels of leptin in infertile patients with or without chronic epididymitis. Experimental epididymitis models were generated by administrating 200 μg Lipopolysaccharide (LPS) to Sprague-Dawley rats. The expression of leptin in epididymis were detected using qPCR, Western blots 6-72 h after injection, and using immunohistochemistry 72 h after injection. Besides, rat epididymal epithelial cells were isolated as an in vitro model and were treated with leptin (5-40 ng/ml, 6-48 h), LPS (1ug/ml, 6 h), and NLRP3 inflammasome inhibitor MCC950 (10 μM, 2 h). Cell Counting Kits-8 assay and Annexin V/PE assay were used to evaluate cell viability and apoptosis. Quantitive PCR and ELISA assay were used to detected inflammatory cytokines interleukin-1beta (IL-1β) production. Western Blots were used to detect molecular related to cell apoptosis, IL-1β maturation, and NLRP3 inflammasome. We found that patients with chronic epididymitis presented a significantly higher level of seminal plasma leptin and correlated declined sperm progressive motility. Leptin and leptin receptor expression in epididymis was significantly upregulated 24 h after LPS administration both in mRNA and protein level, and highly expressed in the epididymis epithelium 72 h after LPS administration. In epididymal epithelial cells, leptin reduced cell viability and promoted apoptosis in a concentration-dependent manner via cleavage of caspase-9, caspase-3, and PARP. Leptin enhanced the LPS-induced production of IL-1β, which was associated with increased IL-1β maturation and caspase-1 activation. Furthermore, NLRP3 inhibitor MCC950 attenuated the effects of leptin or co-treatment with LPS on NLRP3, ASC expression, IL-1β maturation, and caspase-1 activation, which indicated that leptin promotes IL-1β production via activating the NLRP3 inflammasome. These data suggested that leptin may act as a potential evaluation and treatment target for epididymitis and male subfertility.

Topics: Animals; Apoptosis; Cells, Cultured; Epididymis; Epididymitis; Epithelial Cells; Humans; Inflammasomes; Interleukin-1beta; Leptin; Lipopolysaccharides; Male; NLR Family, Pyrin Domain-Containing 3 Protein; Rats, Sprague-Dawley; Up-Regulation

The aim of this study was to ascertain the associations between serum leptin levels and chronic epididymitis and semen parameters in patients with infertility.. A total of 846 patients who were diagnosed as primary infertility were enrolled and divided into four groups. The general information, blood lipids, reproductive hormones, and semen parameters were collected. Receiver operating characteristic (ROC) curves of leptin were plotted for diagnosis of the poor sperm quality. We used Student's t test and the chi-squared test to analyze their relationships and used logistic regression analysis to evaluate potential confounding factors.. Receiver operating characteristic curve revealed that leptin had better sensitivity and specificity at the concentration of 6.02 (0.565 and 0.917). Isolated epididymitis or elevated leptin had no effect on sperm concentration and sperm membrane function, but the combination of these conditions would reduce the concentration and normal morphology rate both (P = 0.002, P = 0.005). Epididymitis or elevated leptin can affect the motility of sperms, the former presented more significance (P = 0.000), and the co-existence would further reduce the sperm motility (P = 0.001).. Low sperm motility and sperm normal morphology were found to be associated with chronic epididymitis and high leptin. Simultaneously suffering from chronic epididymitis and high leptin could produce a more serious effect on sperm quality.

Topics: Adult; Epididymitis; Humans; Infertility, Male; Leptin; Lipids; Male; Semen; Semen Analysis; Spermatozoa; Young Adult