D-galactose (DG)-induced rodent aging model has widely been used for the study of age-related dysfunctions of various organs, including gonads and uterus. Antidiabetic drug metformin has gained an attention as antiaging drug in model organism and human but its effect on uterus has not been studied in relation to induced aging. Therefore, we investigated the effect of metformin on uterus of DG-induced aging mice model. Mice were randomly divided into three groups, that is, control (CN), DG-induced aging model and aging model treated with metformin. Histomorphometric results showed significantly decreased number of uterine glands, endometrial thickness, and increased luminal epithelium height in aging model. Furthermore, metformin resumed the number of uterine glands, endometrial thickness, and luminal epithelium height up to CN group. Metformin has also significantly decreased the ageassociated oxidative stress (malondialdehyde and lipid hydroperoxide). Superoxide dismutase was significantly decreased in both treated groups compared to the CN group. However, catalase and glutathione peroxidase enzymes were significantly increased by metformin compared to the aging model. Immunostaining of active caspase3 and BAX were intense in the endometrium of aging model compare to CN-and metformin-treated groups. Localization of B-cell lymphoma 2 (Bcl2) showed intense immunostaining in the uterus of CN-and metformin-treated groups, with mild immunostaining in aging model. Our observations suggested that metformin treatment might be helpful for management of age-associated uterine dysfunctions.Moreover, it may be concluded that metformin might ameliorate uterine dysfunctions by reducing oxidative stress, suppressing apoptosis, and increasing the survival/ antiapoptotic protein Bcl2.

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Cadmium (Cd) is one of the heavy metal pollutants present in the environment due to human intervention. It is well known that Cd causes toxicological effects on various organs, including the testes. Morin hydrate is a plant‐derived bioflavonoid with antioxidant, anti‐inflammatory, and anti‐stress properties. Thus, the question can be raised as to whether Morin has an effect on Cd‐intoxication‐induced testicular impairment. Therefore, the aim of this study was to investigate the role of Morin on Cd‐mediated disruption of testicular activity. Mice were divided into three groups: group 1 served as the control group, group 2 was given Cd (10 mg/kg) orally for 35 days, and group 3 was given Cd and Morin hydrate (100 mg/kg) for 35 days. To validate the in vivo findings, an in vitro study on testicular explants was also performed. The results of the in vivo study showed that Cd‐intoxicated mice had testicular disorganization, reduced circulating testosterone levels, decreased sperm density, and elevated oxidative stress and sperm abnormality. The expression of the germ cell proliferation marker, germ cell nuclear acidic protein (GCNA), and adipocytokine visfatin were also downregulated. It was observed that Morin hydrate upregulated testicular visfatin and GCNA expression in Cd‐intoxicated mice, along with improvement in circulating testosterone, testicular histology, and sperm parameters. Furthermore, the in vitro study showed that Cd‐mediated downregulation of testicular visfatin and GCNA expression, along with the suppressed secretion of testosterone from testicular explants, was normalized by Morin treatment, whereas visfatin expression was not. Overall, these data indicate that environmental cadmium exposure impairs testicular activity through downregulation of visfatin and GCNA expression, and Morin might play a protective role against Cd‐induced testicular toxicity.