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Human sperm motility-enhancing agents have detrimental effects on mouse oocytes and embryos
1Division of Reproductive Endocrinology, Sinai Hospital of Baltimore, Maryland 21215.
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.
Insights
Sperm motility agents like pentoxifylline and caffeine can artificially activate mouse oocytes but also inhibit embryo development. These agents show toxicity to oocytes and embryos, necessitating caution in human IVF applications.
Area of Science:
- Reproductive Biology
- Developmental Biology
- Assisted Reproductive Technology
Background:
- Human sperm motility-enhancing agents are used in in vitro fertilization (IVF).
- The effects of these agents on oocytes and embryos are not fully understood.
- Pentoxifylline, caffeine, 2-deoxyadenosine, and cyclic adenosine 3':5' monophosphate (cAMP) are common agents.
Purpose of the Study:
- To evaluate the artificial activation potential of sperm motility agents on mouse oocytes.
- To determine the inhibitory effects of these agents on early mouse embryo development.
- To assess the toxicity of these agents to oocytes and embryos.
Main Methods:
- Mouse oocytes were exposed to varying concentrations and durations of pentoxifylline, caffeine, 2-deoxyadenosine, and cAMP.
- Oocyte activation and subsequent embryo development were monitored over 96 hours.
- Controls included ethanol activation and aged oocytes; embryos were cultured with agents at different concentrations.
Main Results:
- Pentoxifylline, caffeine, and 2-deoxyadenosine, but not cAMP, induced artificial oocyte activation in a dose- and time-dependent manner.
- Activated oocytes showed limited developmental potential compared to controls.
- All tested agents exhibited dose-dependent inhibition of embryo development and embryotoxicity, often appearing after several cell cycles.
Conclusions:
- Sperm motility agents can adversely affect mouse oocytes and embryos at concentrations used in human IVF.
- Caution is advised when using these agents in human IVF due to potential toxicity and developmental inhibition.
- Further investigation into the direct effects of these agents on human gametes and embryos is warranted.