Establishment of a varicocele mouse model, and characterization of varicocele-induced inflammation in testis and epididymis; insight into immune cell infiltration, and acute and chronic chemokine and cytokine expression

Abstract

Varicocele (VCL) multi-pathologically affects testicular tissue, epididymis, and consequently sperm fertilizing parameters. The VCL-induced inflammation in association with VCL-induced oxidative stress has been highlighted as the most important VCL-induced pathophysiologies impacting male fertility. Although the increase of inflammatory cytokine levels in both testicular tissue and seminal fluid in VCL condition has been demonstrated by numerous studies, there is no information about cytokine levels in the epididymis, chemokine alteration in testis and epididymis, and leukocyte population changes following VCL. Moreover, there is currently no established murine model of VCL, limiting access to transgenic mouse models. Thus, the current research project aims: 1) to establish a novel VCL model in mice, and 2) to fully understand VCL-induced pro-inflammatory cytokine and chemokine increase, by determining their origin, and effects in testis and epididymis. Moreover, it is important to investigate testicular leukocyte involvement and possible impacts on VCL-induced damages in the testis and epididymis as well as sperm content (spermatogenesis) and functional characteristics. Specifically, we will use flow cytometry, quantitative PCR analysis and CASA (computer assisted sperm analysis) to quantify VCL-induced inflammatory chemokines and cytokines, assess leukocyte and macrophage infiltration in a time-dependent manner in mouse testis and epididymis, and determine the consequence of VCL on sperm fertilizing capacity. The study will be conducted at day 7, 14, 21, 28, and 35 post-VCL, a time period that will cover a full spermatogenesis cycle. At the completion of this study, we will have gained insights on the cellular mechanisms that trigger inflammation and determine the consequence of this inflammation on sperm fertilization parameters following VCL. This study will shed a new light on the clinical assessment of patients suffering from VCL.