MP01-02 PROTEOMIC ANALYSIS OF SEMINAL FLUID IN RHESUS MACAQUES EXPOSED TO DELTA-9-TETRAHYDROCANNABINOL (2023)

You have accessJournal of UrologyCME1 Apr 2023MP01-02 PROTEOMIC ANALYSIS OF SEMINAL FLUID IN RHESUS MACAQUES EXPOSED TO DELTA-9-TETRAHYDROCANNABINOL Jasper C. Bash, Lyndsey E. Shorey-Kendrick, Carol B. Hannah, Charles A. Easley, Eliot Spindel, Jamie O. Lo, and Jason C. Hedges Jasper C. BashJasper C. Bash More articles by this author , Lyndsey E. Shorey-KendrickLyndsey E. Shorey-Kendrick More articles by this author , Carol B. HannahCarol B. Hannah More articles by this author , Charles A. EasleyCharles A. Easley More articles by this author , Eliot SpindelEliot Spindel More articles by this author , Jamie O. LoJamie O. Lo More articles by this author , and Jason C. HedgesJason C. Hedges More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003212.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Cannabis use has been associated with male infertility, but the etiology is not well understood. Seminal fluid is comprised of multiple factors (e.g. proteins), that influence fertility. Our objective was to determine the impact of chronic delta-9-tetrahydrocannabinol (THC) use on the seminal fluid proteome in a rhesus macaque (RM) model. METHODS: 6 adult RMs were given a daily THC edible over 280 days (∼4 spermatogenesis cycles) with serial non-sedated semen collection. Differential expression of proteins in the seminal fluid at baseline (pre-THC), high-THC dose (2.5 mg/7 kg/day), and post-THC discontinuation for 140 days (∼2 spermatogenesis cycles) was evaluated. Proteomic analysis was performed by liquid chromatography tandem mass spectrometry followed by statistical analysis to identify differentially expressed proteins. RESULTS: Proteomic analysis resulted in 1,395 quantifiable proteins (Figure 1A). The average percent identity was 88.6% (SD=14.9%). All RM proteins were matched to human proteins with 99.4% of the RM proteins (1,386) exceeding an identity cutoff of 44.3% (average minus 3 SDs). 7 proteins reached FDR significance in any contrast, thus we focused downstream analyses on nominally significant candidate proteins. Ingenuity Pathway Analysis (Figure 1B) revealed that high-THC exposure was associated with dysregulation of pathways related to “Remodeling of Epithelial Adherens Junctions”, “Axonal Guidance Signaling”, and “Glucocorticoid Receptor Signaling”. THC discontinuation for 140 days was associated with decreased “LXR/RXR Activation”, “Acute Phase Response Signaling”, and “Production of Nitric Oxide and ROS in Macrophages”. 5 proteins dysregulated with THC and significantly restored to baseline included products of CHIT1, FGG, MMP9, TGFBI, and CFB genes (Figure 1D). CHIT1 has been associated with oligozoospermia and MMP9 protein with sperm motility. CONCLUSIONS: This study demonstrated the translational strength of the RM model to study male reproductive health; there was significant seminal fluid proteome homology between humans and RMs. THC-exposed RMs are likely to exhibit proteins in their seminal ejaculate that are involved in regulatory processes that could potentially contribute to male infertility. Source of Funding: OHSU Faculty SEED Award and ASRM Pilot and Exploratory Grant © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jasper C. Bash More articles by this author Lyndsey E. Shorey-Kendrick More articles by this author Carol B. Hannah More articles by this author Charles A. Easley More articles by this author Eliot Spindel More articles by this author Jamie O. Lo More articles by this author Jason C. Hedges More articles by this author Expand All Advertisement PDF downloadLoading ...