Rapamycin protects Sertoli cells against BPA-induced autophagy disorders

Food Chem Toxicol. 2024 Feb 14:114510. doi: 10.1016/j.fct.2024.114510. Online ahead of print.ABSTRACTBisphenol A (BPA) is a well-known environmental contaminant that can negatively impact reproductive function. Disruption of autophagy is implicated in BPA-induced cell injury, the specific molecular mechanisms through which BPA affects autophagy in Sertoli cells are still unknown. In the present study, TM4 cells were exposed to various doses of BPA (10, 100, and 200 μM), and the results indicated that BPA exposure led to the accumulation of autophagosomes, this change was accompanied by increased expression of p-mTOR and decreased expression of Atg12, a protein involved in regulating autophagy initiation. Additionally, BPA exposure upregulated the expression levels of p62, a protein involved in autophagic degradation. The inhibition of autophagy initiation and autophagic degradation contributes to the accumulation of autophagosomes. Further studies showed that BPA exposure didn't affect the expression of the lysosome protein LAMP1; however, decreased cytoplasmic retention of acridine orange in TM4 cells may explain the disruption of autophagy. The role of rapamycin and chloroquine (CQ), an autophagy inhibitor that impairs lysosomal degradation also confirmed the effect of BPA on autophagy regulation. Specifically, rapamycin can protect Sertoli cells against BPA-induced cell injury by promoting autophagy. These findings contribute to our understanding of the mechanisms underly...
Source: Food and Chemical Toxicology - Category: Food Science Authors: Source Type: research