Gold nanoparticles retrogradely penetrate through testicular barriers via Sertoli-cells mediated endocytosis/exocytosis and induce immune response in mouse

Despite the rapidly growing interest in nanoparticle-mediated controllable male contraception and recovery of male fertility, novel applications of nanoparticles in these processes are limited by a knowledge gap regarding their transport and distribution in the testes. Here, we investigated the fate of gold nanoparticles in the mouse testes using two injection methods, namely, interstitial testicular injection (IT-AuNPs, AuNPs exposure in the interstitial compartment of the testes) and rete testis injection (RT-AuNPs, AuNPs exposure in the adluminal compartment of the seminiferous tubules). In this study, we used 100 nm spherical AuNPs and microinjected with 5 μL AuNPs (30 mg/mL) for the experiments. For IT-AuNP injection, we found that AuNPs could not penetrate through the Sertoli cell-mediated blood-testis barrier (BTB) of the seminiferous tubules, and no male reproductive toxicity was observed. For RT-AuNP injection, AuNPs could be retrogradely transported from the adluminal compartment to the interstitial compartment of the testes via Sertoli cell-mediated endocytosis/exocytosis, resulting in damage and the release of inflammatory cytokines in the mouse testis. Our results highlight a retrograde nanoparticle transport function of Sertoli cells, thereby providing a mechanistic overview of the development and use of nanobiotechnology in male reproduction. SYNOPSIS: This study provides new insights into male reproductive immunotoxicity for AuNPs exposure and elucidates a mechanism via Sertoli cell-mediated endocytosis/exocytosis.