Propolis extract nanoparticles alleviate diabetes-induced reproductive dysfunction in male rats: antidiabetic, antioxidant, and steroidogenesis modulatory role.

Diabetes can affect male fertility via oxidative stress and endocrine system disruption. Nanomedicine based on natural products is employed to address diabetes complications. The current study aims to investigate the potential beneficial effect of propolis extract nanoparticles against diabetes-induced testicular damage in male rats. Sixty male rats were randomly allocated to six groups (n = 10). The first group served as a control group. The second and third received propolis extract (Pr) and propolis extract nanoparticles (PrNPs). The fourth group is the diabetic group that received streptozotocin (STZ) (55 mg kg/bwt) single-dose i/p. The fifth and sixth groups are diabetic rats treated with Pr and PrNPs. Both Pr and PrNPs were received at a dose (100 mg/kg bwt) orally. After 60 days, animals were euthanized, then pancreatic and testicular tissues were collected for redox status evaluation, gene expression analysis, and histopathological examination. Also, hormonal analysis (Insulin, total testosterone, and luteinizing hormone (LH) ) along with semen quality evaluation were done. Results showed that the induction of diabetes led to testicular and pancreatic redox status deterioration showing a reduction in reduced glutathione (GSH) as well as elevation of malondialdehyde (MDA), and nitric oxide (NO) levels. Also, relative transcript levels of testicular cytochrome P450 family 11 subfamily A member 1 (CYP11A1), 3β-Hydroxysteroid dehydrogenase (HSD-3β), and nuclear factor (erythroid-derived 2)-like 2 (NFE2L2) were significantly down-regulated, While the advanced glycation end-product receptor (AGER) relative gene expression was significantly upregulated. Furthermore, hormonal and semen analysis disturbances were observed. Upon treatment with Pr and PrNPs,  a marked upregulation of testicular gene expression of CYP11A1, HSD-3β, and NFE2L2 as well as a downregulation of AGER, was observed. Hormones and semen analysis were improved. In addition, the testicular and pancreatic redox status was enhanced. Results were confirmed via histopathological investigations. PrNPs outperformed Pr in terms of steroidogenesis pathway improvement, testicular antioxidant defense mechanism augmentation, and prospective antidiabetic activity.