Silica nanoparticles suppressed the spermatogenesis via downregulation of miR-450b-3p by targeting Layilin in spermatocyte of mouse

Abstract

Silica nanoparticles (SiNPs) suppressed spermatogenesis leading to male reproductive toxicity, while the precise mechanism remains uncertain. Here, this study explored the role of miR-450b-3p in male reproductive toxicity induced by SiNPs. In vivo study, we found that SiNPs caused apoptosis of spermatocytes, decreased quantity and quality of sperms, up-regulated the cytoskeleton proteins (Layilin, Talin, and Vinculin), activated the Hippo pathway (Rho A, Yap, and p73), downregulated the expression of miR-450b-3p, damaged the compactness and density of desmosomes between spermatocytes and the basal of the testis. Moreover, in vitro study, we confirmed that SiNPs increased the expressions of cytoskeleton proteins, activated the Hippo pathway, and suppressed miR-450b-3p expressions. Meanwhile, miR-450b-3p mimic inhibited the up-regulation of cytoskeleton proteins, suppressed the activation of the Hippo pathway, and relieved the adhesion and traction stress. Eventually, atomic force microscopy (AFM) was performed to validate the traction stress and adhesion between GC-2spd cells enhanced by deregulation of miR-450b-3p. Taken together, we concluded that SiNPs suppressed spermatogenesis via inhibiting miR-450b-3p, in turn up-regulating the expression of cytoskeleton proteins, then inducing apoptosis via activating the Hippo pathway and enhancing the traction force and adhesion between GC-2spd cells. This work provides novel evidence for the study of reproductive toxicity and risk assessment of SiNPs.