Effects of Excess Copper Ions on Decidualization of Human Endometrial Stromal Cells.

The aim of this study was to investigate the effects of copper ions on decidualization of human endometrial stromal cells (HESCs) cultured in vitro. Firstly, non-toxic concentrations of copper D-gluconate were screened in HESCs based on cell activity. Then, the effects of non-toxic concentrations of copper ions (0~250 µM) were examined on decidualization of human endometrial stromal cells. Our data demonstrated that the mRNA expressions of insulin-like growth factor binding protein (IGFBP-1), prolactin (PRL), Mn-SOD, and FOXO1were down-regulated during decidualization following the treatments with 100 or 250 µM copper ions. Meanwhile, the amount of malonaldehyde (MDA) in the supernatant of HESCs was increased. These results showed that in vitro decidualization of HESCs was impaired by copper treatment.

Copper-Induced Spermatozoa Head Malformation Is Related to Oxidative Damage to Testes in CD-1 Mice.

The molecular mechanism for copper toxicity on spermatozoa quality in mice is not well understood. In a 4-week experiment, we challenged 24, 6-week-old male CD-1 mice with twice-a-week intraperitoneal copper chloride injections and evaluated spermatozoa quality, copper levels in the testes, serum testosterone, the expression of key antioxidant glutathione peroxidase 5 (GPx5), and the regulated androgen receptor (AR) in the mice testes. We compared these outcomes for four groups of six mice given doses of 0, 1.25, 2.5, 5.0 mg/kg weight copper chloride twice a week for 4 weeks. The mice demonstrated a copper increase spermatozoa head malformation in a dose-response manner. However, we observed no changes in spermatozoa viability and acrosome integrity in the ratio of mouse body weight to testes weight or in the histomorphology of the testes as the average copper level increased. Results of our RT-PCR assays, immunohistochemical tests, ELISA, and histochemistry analyses indicated that testis GPx5 expression was increased, AR expression in the testes was decreased, serum testosterone was decreased, and the activity of 3ß-hydroxysteroid dehydrogenase was decreased as the copper dose increased. In conclusion, these data show that sublethal exposure to copper induces spermatozoa head malformation and influences both mRNA and protein levels of GPx5 and AR which is related to copper resides in the testes.