Bone marrow mesenchymal stem cells repair hexavalent chromium‐induced testicular injury by regulating autophagy and ferroptosis mediated by the AKT/mTOR pathway in rats

Abstract There is no ideal therapy for testicular damage induced by Cr(VI); however, bone marrow mesenchymal stem cells (BMSCs) transplantation may be a promising therapy. A Cr(VI) solution was administered to rats by intraperitoneal injection for 30 days, then BMSCs from donor rats were transplanted. Two weeks later, decreased activity and appetite, along with other pathological changes, were improved in the BMSCs group. The location of BMSCs in damaged testes was observed via laser confocal microscopy. Chromium content in the Cr(VI) and BMSCs groups significantly increased compared with that in the control group, but there was no significant difference between the two groups, as revealed by atomic absorption spectrometry. The ferrous iron and the total iron content of testes in the BMSCs group were significantly lower than those in the Cr(VI) group, as observed by Lillie staining and a tissue iron assay kit. Western blotting and immunohistochemical analyses revealed that the expression of Beclin 1, LC3B, 4‐hydroxynonenal, and transferrin receptor 1 was decreased in the BMSCs group, compared with the Cr(VI) group. The expression of glutathione peroxidase 4 (GPX4), SLC7A11, p‐AKT, mammalian target of rapamycin (mTOR), and p‐mTOR in the BMSCs group was higher than that in the Cr(VI) group. Taken together, we propose that BMSCs repair Cr(VI)‐damaged testes by alleviating ferroptosis and downregulating autophagy‐associated proteins through the upregulation of AKT and mTOR phosphorylation.