Present study demonstrated that fibrillar β-amyloid peptide (fAβ 1-42 ) induced ATP release, which in turn activated NADPH oxidase via the P2X 7 receptor (P2X 7 R). Reactive oxygen species (ROS) production in fAβ1-42-treated microglia appeared to require Ca 2+ influx from extracellular sources, because ROS generation was abolished to control levels in the absence of extracellular Ca 2+. Considering previous observation of superoxide generation by Ca 2+ influx through P2X 7 R in microglia, we hypothesized that ROS production in fAβ-stimulated microglia might be mediated by ATP released from the microglia. We therefore examined whether fAβ1-42-induced Ca 2+ influx was mediated through P2X 7 R activation. In serial experiments, we found that microglial pretreatment with the P2X 7 R antagonists Pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate (100 µM) or oxidized ATP (100 µM) inhibited fAβ-induced Ca 2+ influx and reduced ROS generation to basal levels. Furthermore, ATP efflux from fAβ1-42-stimulated microglia was observed, and apyrase treatment decreased the generation of ROS. These findings provide conclusive evidence that fAβ-stimulated ROS generation in microglial cells is regulated by ATP released from the microglia in an autocrine manner.

This study was performed to investigate the effect of of transdermal testosterone gel (TTG) on controlled ovarian stimulation (COS) and IVF outcomes and ovarian morphology according to pretreatment duration in poor responders. A total of 120 women were recruited for this pilot study. They were randomized into control, 2 weeks, 3 weeks or 4 weeks TTG treatment groups. For three TTG treatment groups, 12.5 mg TTG was applied daily for 2 weeks, 3 weeks or 4 weeks in preceding period of study stimulation cycle. After 3 weeks of TTG pretreatment, significant increase of antral follicle count (AFC) and significant decreases of mean follicular diameter (MFD) and resistance index (RI) value of ovarian stromal artery were observed (p=0.026, p<0.001, p<0.01, respectively). The total dose of rhFSH administered for COS significantly decreased after 3 and 4 weeks TTG treatment both compared with control group (p<0.001, p<0.001). The numbers of oocytes retrieved and mature oocytes were significanty higher in 3 and 4 weeks TTG treatment groups than control group (p<0.001, p<0.001 in the number of oocytes retrieved; p<0.001, p<0.001 in the number of mature oocytes). The clinical pregnancy rate and live birth rate were increased only in 4 weeks TTG treatment group compared with control group (p=0.030 and p=0.042, respectively). These data demonstrated that TTG pretreatment for 3 to 4 weeks increases AFC and ovarian stromal blood flow, thereby potentially improving the ovarian response to COS and IVF outcome in poor responders undergoing IVF/ICSI.

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