BECLIN-1-Mediated Autophagy Suppresses Silica Nanoparticle-Induced Testicular Toxicity via the Inhibition of Caspase 8-Mediated Cell Apoptosis in Leydig Cells

• Published in: Cells (Basel, Switzerland) Vol. 11; no. 12; p. 1863
• Main Authors: Zhang, Qianru, Grunberger, Jason William, Khurana, Nitish, Zhou, Xin, Xu, Xianyu, Ghandehari, Hamidreza, Chen, Fenglei
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 07.06.2022; MDPI
• Subjects: Antibodies; Apoptosis; Autophagy; Bcl-2 protein; BECLIN-1; Caspase-3; Caspase-8; Cell viability; Chloroquine; Cholecystokinin; Ethanol; Flow cytometry; Investigations; Leydig cells; Microscopy; Nanoparticles; Proteins; Rapamycin; silica nanoparticles; Spermatogenesis; Testes; testicular toxicity; Toxicity; Western blotting; United States > US; China
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells11121863

Accumulation of silica nanoparticles (SNPs) in the testes leads to male reproductive toxicity. However, little is known about the effect and mechanistic insights of SNP-induced autophagy on apoptosis in Leydig cells. In this study, we aimed to verify the role of SNP-induced autophagy in apoptosis and explore the possible underlying mechanism in mouse primary Leydig cells (PLCs). H&E staining showed that SNPs changed the histological structures of the testes, including a reduction in the Leydig cell populations in vivo. CCK-8 assay showed that SNPs decreased cell viability, and flow cytometry showed that SNPs increased cell apoptosis, both in a dose-dependent manner in vitro. Additionally, Western blotting further found that SNPs activated autophagy by an increase in BECLIN-1, ATG16L, and LC3-II levels and promoted the intrinsic pathway of apoptosis by an increase in the BAX/BCL-2 ratio, cleaved the caspase 8 and caspase 3 levels. Furthermore, autophagy decreased SNP-induced apoptosis via regulation of the caspase 8 level combined with rapamycin, 3-methyladenine, and chloroquine. BECLIN-1 depletion increased the caspase 8 level, leading to an increase in SNP-induced cell apoptosis. Collectively, this evidence demonstrates that SNPs activated BECLIN-1-mediated autophagy, which prevented SNP-induced testicular toxicity via the inhibition of caspase 8-mediated cell apoptosis in Leydig cells.