Phosphodiesterase 3 inhibitors selectively block the spontaneous resumption of meiosis by macaque oocytes in vitro.
BACKGROUND
The purpose of this study was to determine whether phosphodiesterase (PDE) 3 inhibitors selectively prevent the resumption of meiosis in primates.


METHODS
Immature oocytes (intact germinal vesicles) obtained from large pre-ovulatory follicles following ovarian stimulation in rhesus macaques were incubated with or without various doses of the PDE3 inhibitors, Cilostamide, Milrinone or ORG 9935, or a selective PDE4 inhibitor, Rolipram. Oocytes were observed for germinal vesicle breakdown (GVBD) as an indicator of resumption of meiosis.


RESULTS
At 24 h, 72 of 121 (60%) control oocytes progressed to GVBD compared with 9/34 (27%, P < 0.01), 4/36 (11.1%, P < 0.01) and 0/28 (0%, P < 0.01) oocytes incubated with ORG 9935 at 0.1, 0.5 and 1.0 micromol/l respectively. Similar results were achieved at 24 h with 1.0 micromol/l Cilostamide (2/24 oocytes, 8%, P < 0.01) and 100 micromol/l Milrinone (2/32, 6%, P < 0.01). In contrast, no significant difference in GVBD was noted between control oocytes and those incubated with up to 100 micromol/l Rolipram for 24 h (43/58, 74%) or 48 h (44/58, 76%).


CONCLUSIONS
These experiments establish the specificity and dose-dependent ability of PDE3, but not PDE4, inhibitors to block resumption of meiosis in macaque oocytes in vitro. Thus, PDE3 inhibitors have potential use as contraceptives in primates.
Jensen
J T
JT
Department of Obstetrics and Gynecology and Division of Reproductive Sciences, Oregon Regional Primate Research Center, Oregon Health & Science University, Portland, OR 97201, USA. jensenje@ohsu.edu
Schwinof
K M
KM
Zelinski-Wooten
M B
MB
Conti
M
M
DePaolo
L V
LV
Stouffer
R L
RL
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D002478:Cells, Cultured; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D005240:Feasibility Studies; D005260:Female; D008253:Macaca mulatta; D008540:Meiosis / Q000187:drug effects*; D020105:Milrinone / Q000494:pharmacology; D009865:Oocytes / Q000166:cytology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology; D020889:Rolipram / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology
D010726:Phosphodiesterase Inhibitors; D015363:Quinolones; D013876:Thiophenes; C097915:Org 9935; C021294:cilostamide; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020105:Milrinone; D020889:Rolipram