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Role of spermatozoal platelet-activating factor in fertilization
F B Kuzan1, F T Geissler, W R Henderson
1Department of Obstetrics and Gynecology, University of Washington, Seattle 98195.
Abstract:
Platelet-activating factor (PAF), a potent lipid mediator of inflammation, has been shown to play a role in both the implantation and viability of mammalian embryos. We examined whether human and mouse spermatozoa release PAF during in vitro incubation and assessed the effect of exogenous PAF and the PAF receptor antagonist WEB 2086, a thieno-triazolodiazepine, on mouse in vitro fertilization (IVF) rate. PAF biological activity was detected in 11 samples of leukocyte-free, purified human spermatozoa (28 pg PAF/10(6) cells/24 hr) and 5 samples of epididymal mouse spermatozoa (7.8 pg PAF/10(6) cells/3 hr). Exogenous PAF (10(-8) and 10(-6) M) increased (p less than 0.01) the fertilization rate 2- and 3-fold, respectively of mouse oocytes by mouse epididymal spermatozoa. 10(-4) M PAF, however, reduced sperm motility and decreased (p less than 0.05) the fertilization rate. 10(-6) M WEB 2086, decreased IVF to approximately 50% of the control fertilization rate (42% vs. 89%). WEB 2086 treatment also promoted the attachment of supernumerary spermatozoa to both fertilized and unfertilized oocytes. The fertilization rate in the presence of WEB 2086 returned to control levels when zona-pellucida-free oocytes were employed, indicating that WEB 2086 did not interfere with the spermatozoal acrosome reaction. These data suggest that PAF, of spermatozoal origin, may be important in mammalian fertilization.
Insights
Platelet-activating factor (PAF) is released by human and mouse sperm, enhancing fertilization. Blocking PAF receptors reduces fertilization rates, suggesting PAF
Area of Science:
- Reproductive Biology
- Cell Signaling
- Immunology
Background:
- Platelet-activating factor (PAF) is a key inflammatory mediator.
- PAF influences mammalian embryo implantation and viability.
- The role of PAF in mammalian fertilization is not fully understood.
Purpose of the Study:
- To investigate PAF release by human and mouse spermatozoa.
- To determine the effect of exogenous PAF on mouse in vitro fertilization (IVF).
- To assess the impact of a PAF receptor antagonist (WEB 2086) on mouse IVF.
Main Methods:
- Detection of PAF in purified human and mouse spermatozoa.
- In vitro fertilization assays using mouse oocytes and spermatozoa.
- Administration of varying concentrations of PAF and WEB 2086.
- Evaluation of fertilization rates and sperm-oocyte interactions.
Main Results:
- PAF was detected in both human and mouse spermatozoa.
- Exogenous PAF (10⁻⁸ and 10⁻⁶ M) significantly increased mouse IVF rates.
- High concentration PAF (10⁻⁴ M) reduced sperm motility and fertilization.
- WEB 2086 (10⁻⁶ M) significantly decreased IVF rates and promoted supernumerary sperm attachment.
- WEB 2086's effects were mitigated in zona-pellucida-free oocytes, suggesting no interference with the acrosome reaction.
Conclusions:
- Spermatozoa release PAF, indicating a potential autocrine or paracrine role.
- PAF appears to play a crucial role in promoting mammalian fertilization.
- Targeting the PAF pathway could offer novel approaches in reproductive medicine.