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Published on: September 15, 2012
Cilostazol blocks pregnancy in naturally cycling mice
Ahmed M Taiyeb Albarzanchi1, Christie M Sayes, Mundhir T Ridha Albarzanchi
1Department of Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA. aridha@cvm.tamu.edu
Background:
Administration of a phosphodiesterase three enzyme inhibitor (PDE3-I) in rodents and primates results in ovulation of immature oocytes. Concerns regarding inhibition of PDE3 enzymes that are expressed in heart and blood vessels discouraged further development of PDE3-Is as nonsteroidal contraceptives. Cilostazol (CLZ) is a PDE3A-I that is approved for medical indications in humans and has an additional effect of adenosine uptake inhibition that is believed to counterbalance the undesirable outcomes resulting from PDE inhibition.
Study Design:
Cycling mature female mice were treated with 7.5 or 15 mg CLZ, dimethyl sulfoxide or water beginning on the day of proestrus. Animals were placed with fertility-proven males after 3 days of treatment. Treatments were continued until 1 day after detection of a vaginal plug, and then females were monitored up to 30 days postbreeding to assess the effects of the compounds on pregnancy. Each of the treated female with CLZ was then remated with the same male and again monitored up to 30 days.
Results:
None of the CLZ-treated mice produced offspring, whereas all of the control animals maintained pregnancy and delivered normal pups (p<.0001). Remating of the previously CLZ-treated females exhibited normal pregnancies and gave birth to live offspring that were not different from the controls.
Conclusion:
CLZ is a potential nonsteroidal contraceptive agent that merits further evaluation in other mammals.
Insights
Cilostazol (CLZ), a PDE3 inhibitor, prevented pregnancy in female mice. However, fertility was restored upon subsequent mating, suggesting CLZ as a potential reversible nonsteroidal contraceptive.
Area of Science:
- Reproductive biology
- Pharmacology
Background:
- Phosphodiesterase three inhibitors (PDE3-Is) can induce ovulation but raise safety concerns due to cardiovascular effects.
- Cilostazol (CLZ), a PDE3A-I approved for human medical use, also inhibits adenosine uptake, potentially mitigating side effects.
Purpose of the Study:
- To evaluate Cilostazol (CLZ) as a potential nonsteroidal contraceptive agent.
- To assess the reversibility of CLZ's contraceptive effects in female mice.
Main Methods:
- Mature female mice received daily doses of CLZ (7.5 or 15 mg), dimethyl sulfoxide, or water.
- Mice were mated with fertile males after 3 days of treatment and monitored for pregnancy.
- Females that did not conceive were remated to assess fertility recovery.
Main Results:
- No CLZ-treated mice maintained pregnancy or produced offspring.
- Control groups successfully maintained pregnancy and delivered pups.
- Previously treated females demonstrated normal pregnancies and live births upon remating, indicating reversible effects.
Conclusions:
- Cilostazol (CLZ) exhibits potential as a nonsteroidal contraceptive agent.
- The contraceptive effects of CLZ appear to be reversible.
- Further evaluation in other mammalian species is warranted.
