Cilostazol blocks pregnancy in naturally cycling swine: An animal model

Abstract

Aims: Cilostazol (CLZ) is an FDA approved therapeutic that is indicated for patients with intermittent claudication disease. CLZ is a selective inhibitor for phosphodiesterase 3A (PDE3A); an enzyme that controls oocyte maturation in many mammals including humans. Recently, CLZ has been reported to block pregnancy and oocyte maturation in mice. The objective of the present work was to evaluate the potential non-steroidal contraceptive capacity of CLZ using a more advanced translational model for humans.

Main methods: Three groups of naturally cycling sows were treated orally with 0, 100, or 200mg CLZ, twice a day (bid), for 6days before estrus and continued for three days after estrus. Each sow was mated by one of two proven fertile boars on alternate days during estrus.

Key findings: CLZ dose of 100mg, bid, completely blocked pregnancy in sows when compared to control sows (P<0.01). However, the 200mg dose of CLZ, bid, failed to significantly block pregnancy in pigs. No significant differences were observed in heart rates of treated and control animals. Re-mating of the previously treated sows exhibited normal pregnancies and litter sizes.

Significance: This study shows that CLZ is capable of producing a reversible non-steroidal contraceptive effect without adverse effects on the heart rate in pigs. The observed contraceptive effect of CLZ was at doses similar to those indicated to humans. This FDA approved agent, for treatment of patients with intermittent claudication, may have an additional therapeutic effect as a non-steroidal contraceptive agent. Cilostazol merits further evaluation in women and might be useful for controlling the population of homeless animals.

Keywords: Cilostazol; Contraceptive; Fertility; Oocyte maturation; Swine.