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In vitro effect of RU 486 on sperm-egg interaction in mice
1Department of Obstetrics and Gynecology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City 37614.
Abstract:
The effect of RU 486 at different concentrations (1, 5, 10, and 20 micrograms/ml) was studied on sperm-egg interaction in vitro in B6D2F1 mice. The in vitro fertilization rate of mouse ova decreased from 77.0% (control) to 50.0%, 28.7%, and 7.5% in the presence of RU 486 concentrations at 5, 10, and 20 micrograms/ml medium, respectively (p less than 0.001). A concentration of 1 microgram/ml did not affect the fertilization rate. A progesterone concentration at equal to or double the concentration RU 486 did not reverse the inhibitory effect of RU 486 on in vitro fertilization, which suggests a progesterone-independent mechanism. Exposure of spermatozoa (for 90 minutes) or ova (for 60 minutes) to RU 486 (20 micrograms/ml) followed by washing with RU 486-free medium before coincubation did not affect the fertilization rate. The presence or absence of cumulus cells did not change the inhibitory effect of RU 486 (20 micrograms/ml) on in vitro fertilization. RU 486 at 5 to 20 micrograms/ml medium was associated with perivitelline polyspermy in nonfertilized ova and enhanced perivitelline polyspermy in fertilized ova.
Insights
RU 486 significantly reduces in vitro fertilization rates in mice at concentrations of 5 micrograms/ml and higher. This effect appears independent of progesterone and is linked to increased polyspermy.
Area of Science:
- Reproductive biology
- Endocrinology
- In vitro fertilization research
Background:
- RU 486, a synthetic steroid, is known for its antiprogestogenic and antiglucocorticoid activities.
- Its effects on gamete interaction and fertilization are not fully understood.
- Understanding these effects is crucial for reproductive medicine and toxicology.
Purpose of the Study:
- To investigate the impact of RU 486 on sperm-egg interaction in vitro.
- To determine the dose-dependent effects of RU 486 on fertilization rates.
- To explore the mechanism of RU 486's action on fertilization.
Main Methods:
- In vitro fertilization assays using B6D2F1 mouse sperm and ova.
- Exposure of gametes to varying concentrations of RU 486 (1-20 micrograms/ml).
- Assessment of fertilization rates and polyspermy; testing progesterone reversal and effect of washing/cumulus cells.
Main Results:
- RU 486 significantly inhibited in vitro fertilization rates at concentrations of 5, 10, and 20 micrograms/ml (p < 0.001).
- A concentration of 1 microgram/ml had no significant effect.
- The inhibitory effect was progesterone-independent and not reversed by washing gametes or altering cumulus cell presence.
- Increased perivitelline polyspermy was observed in both fertilized and non-fertilized ova.
Conclusions:
- RU 486 exerts a dose-dependent inhibitory effect on mouse in vitro fertilization.
- The mechanism is likely progesterone-independent and may involve direct effects on gametes or the fertilization process.
- RU 486 exposure is associated with polyspermy, indicating potential disruption of fertilization control mechanisms.