Investigation of the Effect of hUC-MSCs on Autophagy and Apoptosis in Cadmium-Induced Mice Thyroid
Abstract
Objective: Previous studies have showed that cadmium (Cd) induces structural changes in thyroid follicles. Various disorders are treated with human umbilical cord MSCs (hUC-MSCs), which are easily cultured, grown, purified, harvested, and separated. This study aimed to assess how cadmium affects autophagic and apoptotic pathways and protective effects of hUC-MSCs on thyroid gland. Methods: Four groups (n = 6) of C57BL/6 mice were established: control, hUC-MSCs, Cadmium, and Cadmium + hUC-MSCs. Blood samples were collected and analyzed to measure levels of thyroid-stimulating hormone (TSH), triiodothyronine (fT3), and thyroxine (fT4). Hematoxylin-eosin (H&E) and Masson trichrome staining were used to determine histopathological changes. Additionally, the expression levels of apoptotic marker Caspase-3 and autophagic markers Beclin-1, LC3B, p62 were analyzed by immunohistochemistry. Results: The histopathological results showed that Cd exposure resulted in damaged thyroid follicles, vacuoles in follicles, flattening of follicular epithelium, vascular congestion in thyroid tissues, and invasion of follicular connective tissue by mononuclear cells. The histologic structures improved when hUC-MSCs were used to treat thyroid tissues from mice induced with cadmium. There was a difference in degeneration in fibrosis (p < 0.05), and mononuclear cell infiltration (p < 0.05) between the Cd and Cd+hUC-MSCs groups. The findings demonstrated that, in contrast to control mice, Cd exposure raised serum levels of TSH while decreasing the levels of fT3 (p < 0.05) and fT4 (p < 0.01). Furthermore, immunoexpression of Caspase-3 (p < 0.01), Beclin-1 (p < 0.01), LC3B (p < 0.01) was increased; conversely, p62 (p < 0.05) was decreased in Cd-treated thyroid tissue of mice compared to control and hUC-MSCs groups. Conclusions: We conclude that exposure to cadmium induces cellular-level damage in thyroid tissue. Cadmium can also induce apoptosis and is associated with alterations in autophagy-related pathways. hUC-MSCs may mitigate the adverse effects of Cd.