Local therapy for orchitis-induced infertility in rats: Melatonin within thermosensitive nanoplatforms

MAIO MB; FERRER VIÑALS D; MUNDURUCA PIRES T; GLIENKE L; GONZALEZ L; OCAMPO C; LUSTIG L; SOBARZO C; JACOBO P; GLISONI R; THEAS MS

BUENOS AIRES

Congreso; IMBS VI International Congress in Traslational Medicine; 2023

Friburgo-UBA

Introduction: Approximately 30-50% of cases of infertility are due to a male factor; a reduction in the quality of sperm in which oxidative stress plays a significant role. Experimental autoimmune epididymo-orchitis (EAEO) is a well-established rodent model for studying the impact of inflammatory processes and oxidative stress on spermatogenesis associated with infertility. Melatonin (MLT) is an antioxidant and antiapoptotic hormone, and its properties can be harnessed for counteracting the EAEO inflammatory environment. However, it has limited solubility in aqueous medium and short half-life. Pluronic® F127 is a biocompatible nanoplatform of polymeric micelles (PMs) based of PEO-PPO block copolymers exhibiting reverse thermal gelation at body temperature and a concentration higher of 20% (w/v) in biological medium, used for enhancing drug delivery and solubility. Objective: Our aim was to optimize melatonin delivery and improve its availability within the tests, employing Pluronic® F127, thereby exploring its capacity to counteract the impact of oxidative stress on spermatogenesis and sperm quality in EAEO. Material and methods: Animals: Adult male Wistar rats between 300-500 grams Nanoplatform preparation: PMs were prepared by dispersing an adequate amount of F127 copolymer in aqueous medium at 4°C (overnight) to a final volume of 25% (w/v ). Melatonin loading within the nanoplatform: F127 25% (w/v) was combined with a 25 mg/mL of melatonin solution (Saporiti Drugstore) and stirred continuously for 24 hours at 4°C. Sperm analysis: Sperm was obtained from the epididymis cauda and was incubated with Human tubal fluid medium + 4 mg/mL BSA at 37°C for 10 minutes in a thermostatic bath. Viability (eosin staining), motility, sperm count, and morphology (Coomasie blue R staining) were analyzed. Conclusions: Melatonin-F127 25% injected into the testis had a positive effect on stored epididymal sperm through its strong antioxidant properties and also a reduction in inflammatory cells. Our study suggested that local melatonin delivery through thermosensitive polymeric micelles, might be a good strategy to address orchitis-induced male infertility.