Copper nanoparticles lead to reproductive dysfunction by affecting key enzymes of ovarian hormone synthesis and metabolism in female rats.

Studies on the general toxicity of copper nanoparticles (Cu NPs) have been conducted extensively, but their effects on reproductive toxicity remain unclear. In this study, we evaluated the toxic effect of Cu NPs on pregnant rats and their litter. The comparative in vivo toxicity of Cu ions, Cu NPs, and Cu microparticles (MPs) was studied in a 17-day repeated oral-dose experiment at the doses of 60, 120, and 180 mg/kg/day in pregnant rats. The pregnancy rate, mean live litter size, and number of dams decreased when exposed to Cu NPs. Moreover, Cu NPs caused a dose-dependent increase in ovarian Cu levels. The metabolomics results showed that Cu NPs caused reproductive dysfunction by altering sex hormones. In addition, in vivo and in vitro experiments showed that the ovarian cytochrome P450 enzymes (CYP450), responsible for hormone production, were significantly upregulated, whereas the enzymes responsible for hormone metabolism were significantly inhibited, resulting in a metabolic imbalance in some ovarian hormones. Furthermore, the results revealed that the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways significantly participated in the regulation of ovarian CYP enzyme expression. Overall, the results of the in vivo and in vitro toxicity experiments with Cu ions, Cu NPs, and Cu MPs suggested that toxicity from nanoscale Cu particles poses a more serious reproductive threat than microscale Cu as Cu NPs could directly damage the ovary and affect the metabolism of ovarian hormones.

C21 steroidal glycosides from Cynanchum auriculatum and their neuroprotective effects against H2O2-induced damage in PC12 cells.

Twenty-three undescribed previously C21 steroidal glycosides, named saccatols D-K and cynsaccatols I-W, together with six known analogs were isolated from the roots of Cynanchum auriculatum Royle ex Wight (Apocynaceae). Their structures were elucidated by a variety of spectroscopic techniques, as well as HRESIMS and GC method. All isolated compounds were tested their neuroprotective effects on the model of H2O2-induced damage to PC12 cells. Except saccatols D-F, J, cynsaccatol V and wilfoside A, other twenty-three isolates produced significantly activities against H2O2-induced cell damage (P < 0.001). Furthermore, cynsaccatols I, N, O and S can obvious inhibition of damaged PC12 cell apoptosis at their dosages of 1 µM by Annexin V-FITC/PI double staining assay with flow cytometry.