The pharmacological development of non-steroidal contraceptives has yet to be achieved. Arresting oocyte maturation without blocking ovulation has been evaluated using different inhibitors of the phosphodiesterase 3A (PDE3A). Unfortunately, PDE3A is also expressed in the heart and blood vessels, and inhibition of PDE3A in oocytes can produce cardiovascular side effects. We reviewed the literature on available PDE3 inhibitors and selected cilostazol (CLZ), which is an FDA approved therapeutic. CLZ has the ability to decrease cellular adenosine uptake and consequently antagonizes side effects of PDE3A inhibition in vital organs. CLZ inhibited oocyte meiotic maturation in vitro. CLZ has more degenerative impact on arrested oocytes than matured oocytes, indicating that prolonged meiotic arrest of oocytes is harmful. Administration of CLZ any time from 9h before the ovulatory stimulus to 4h after the stimulus resulted in ovulation of immature oocytes. Controlling CLZ dose, time of CLZ administration, and time of oocyte collection resulted in ovulation of oocytes at different meiotic stages. Oral administrations of CLZ in naturally cycling mice were also observed to block pregnancy whereas remating of those previously treated females resulted in normal offspring and litter sizes. Therefore, CLZ does not only have a wide margin of contraception but also is reversible.
Ovulated immature oocytes were observed to have higher rates of advanced chromatin configuration and cortical granule distribution, normal spindle and chromosomal organization, maturation, and in vitro fertilization (IVF) than ovarian immature oocytes. Ovulated metaphase I oocytes that were matured in vitro or in vivo had higher IVF rates than ovulated mature oocytes. Ovulated germinal vesicle (GV) oocytes that were in vitro matured also showed higher IVF rates but when in vivo matured, they had lower IVF rates than ovulated mature oocytes because of the high degeneration and low fertilization rates associated with in vivo maturation of GV oocytes.
In summary, CLZ merits further evaluation as a non-steroidal contraceptive and is capable of producing oocytes of various meiotic stages with advanced developmental features.
| Identifer | oai:union.ndltd.org:tamu.edu/oai:repository.tamu.edu:1969.1/148278 |
| Date | 14 March 2013 |
| Creators | Taiyeb-Ridha, Ahmed 1979- |
| Contributors | Kraemer, Duane C, Fajt, Virginia |
| Source Sets | Texas A and M University |
| Detected Language | English |
| Type | Thesis, text |
| Format | application/pdf |
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