The phosphodiesterase 3 inhibitor ORG 9935 inhibits oocyte maturation in the naturally selected dominant follicle in rhesus macaques.
BACKGROUND
The study was conducted to determine whether the phosphodiesterase (PDE) 3 inhibitor ORG 9935 prevents the resumption of meiosis in primate oocytes during natural menstrual cycles.


METHODS
Regularly cycling adult female macaques (n=8) were followed during the follicular phase and then started on a 2-day treatment regimen of human recombinant gonadotropins to control the timing of ovulation. Monkeys received no further treatment (controls) or ORG 9935. Oocytes were recovered by laparoscopic follicle aspiration 27 h after an ovulatory stimulus, cultured in vitro in the absence of inhibitor and inseminated. The primary outcome was the meiotic stage of the oocyte.


RESULTS
In six ORG 9935 cycles, five of the recovered oocytes were germinal vesicle (GV)-intact, and one exhibited GV breakdown (GVBD). In contrast, all three oocytes that recovered during control cycles were GVBD (p<.05). None of the ORG 9935-treated oocytes underwent fertilization compared with 2/3 (67%) from controls.


CONCLUSIONS
These results demonstrate that ORG 9935 blocks resumption of meiosis in the naturally selected dominant follicle in primates and suggest that PDE3 inhibitors have potential clinical use as contraceptives in women.
Jensen
Jeffrey T
JT
Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR 97239, USA.
Zelinski
Mary B
MB
Stanley
Jessica E
JE
Fanton
John W
JW
Stouffer
Richard L
RL
D000818:Animals; D003271:Contraceptive Agents, Female / Q000494:pharmacology; D005260:Female; D008253:Macaca mulatta; D008540:Meiosis / Q000187:drug effects*; D009865:Oocytes / Q000187:drug effects*; D010060:Ovulation / Q000187:drug effects; D058987:Phosphodiesterase 3 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*
D003271:Contraceptive Agents, Female; D058987:Phosphodiesterase 3 Inhibitors; D010726:Phosphodiesterase Inhibitors; D013876:Thiophenes; C097915:Org 9935