Lipopolysaccharide-induced inflammation modulates testicular kisspeptin system in mice

Kisspeptin, a neuropeptide hormone, plays an indispensable role in regulating reproduction. Acting upstream of gonadotropin-releasing hormone, it controls gonadotropin release, and concomitant gonadal functions, and in turn, is regulated by gonadal steroid hormones. Nevertheless, expression of kisspeptin (Kiss1) and its receptor (Kiss1r) is reported in tissues other than hypothalamus, including testes. Since immune-challenged conditions lead to compromised reproductive functions, the present work emphasizes on investigating regulation of the testicular kisspeptin system in adult mice by lipopolysaccharide (LPS)-induced inflammation. In vivo chronic treatment of LPS for 7 days caused irregularly-shaped seminiferous tubules with reduced perimeter, diameter and cross-sectional area, distorted arrangement of spermatogenic cells, disrupted connective tissue leading to increased interstitial space and reduced sperm count. Further, elevated expression level of pro-inflammatory cytokine, Tnfα, in the testis validated the induction of inflammation. Regarding the kisspeptin system, a significant increase in testicular Kiss1 but a decrease in Kiss1r expression was observed at both gene and protein levels, implying a possible compensatory role of testicular kisspeptin to control reproductive functions under an infectious state. Further, an in vitro treatment of testicular fragments with LPS was conducted for 3 h and 6 h to understand the direct effect of inflammation on the testicular kisspeptin system. An increased Tnfα but decreased Tgfβ1 expression was observed at both time points. At the transcript level, Kiss1 showed a reduced expression at 6 h but no change at 3 h of LPS treatment. Regarding Kiss1r, an increased expression at 3 h but decreased at 6 h was seen. At the protein level, decreased levels of testicular Kiss1 was observed at both the time points while Kiss1r exhibited no significant change. Hence, the present work demonstrated modulation of the testicular kisspeptin system by LPS-induced inflammation.