Role of mononuclear cells, stem cells, and exosomes in hypothyroid testicular dysfunction in rats via modulation of ZO-1, SIRT/FOXO. Focusing on blood testes barrier

Bone marrow mesenchymal stem cells (BMSCs) are stromal cells that can self-renew. Exosomes (EXOs) perform many biological functions particularly in cell-cell communication. Peripheral blood mononuclear cells (PBMNCs) have the ability to differentiate into numerous mature functional cell types in specific microenvironments. This study aimed to compare the possible ameliorating effect of BMSCs, EXOs, and PBMNCs on hypothyroidism-induced testicular damage in adult male rats. Forty‑eight adult male albino rats were divided randomly into five groups: control, hypothyroidism (HT), BMSCs-treated, EXOs-treated, and PBMNCs-treated groups. Testes and thyroids were dissected and prepared for biochemical, histological, and immunohistochemical studies. After induction of HT, the results showed an apparent decrease in testes weight and abnormal semen analysis. Additionally, a significant decrease in antioxidant markers, thickness of the germinal epithelium, PAS staining, and testes BCL2 anti-apoptotic marker. It showed histological changes. Additionally, a significant decrease in SIRT-1 and ZO-1immune stained cells. A significant increase in testes BAX apoptotic marker, FOXO-1 immuno-expression, and deficient blood testes barrier with abnormal spermatogenic cells in electron microscopy were also detected. Improvement in all mentioned parameters in treated groups was noticed. Our study suggested that PBMNCs holds promise for alleviating hypothyroidism in rats on biochemical, histological, and immunohistochemical basis.