Human sperm motility-enhancing agents have detrimental effects on mouse oocytes and embryos

Objectives: To test the artificial activating properties of the human sperm motility-enhancing agents pentoxifylline, caffeine, 2-deoxyadenosine, and cyclic adenosine 3':5' monophosphate (cAMP) on mouse oocytes and determine if the agents exhibit an inhibitory effect on in vitro development of mouse embryos. Design: CD-1 mouse oocytes were exposed to 1, 2.5, 5, or 10 mM pentoxifylline, caffeine, 2-deoxyadenosine, or cAMP for 10, 30, or 60 minutes and their activation and development was scored over 96 hours of culture. A 10% ethanol solution and aging unstimulated oocytes served as controls. Pronuclear embryos from CD-1, CF-1, and B6C3 F1 hybrid mice were cultured in 0.16, 0.33, 0.66, 1.25, 2.5, 5.0, or 10 mM of pentoxifylline, caffeine, 2-deoxyadenosine, or cAMP and development was scored over 96 hours of culture. Results: Exposure to pentoxifylline, caffeine, and 2- deoxyadenosine, but not cAMP, artificially activated mouse oocytes in a concentration- and exposure time-dependent manner. The level of activation was significantly greater than that associated with oocyte aging but less than ethanol-induced activation. Agent-activated oocytes had limited developmental capacity compared with the ethanol-activated oocytes. Pentoxifylline and 2-deoxyadenosine were more toxic than caffeine, especially at the higher concentrations and after prolonged exposure. All of the agents affected embryo development in a dose-dependent manner with developmental inhibition and embryotoxicity that was often not evident until after one to three cell cycles. Conclusions: Pentoxifylline, caffeine, 2-deoxyadenosine, and cAMP have adverse effects on mouse oocytes or embryos at concentrations commonly used to activate sperm in human IVF. Therefore, care should be taken to minimize the exposure of human oocytes and embryos to these agents until their direct effects have been investigated more fully.