Follicular administration of a cyclooxygenase inhibitor can prevent oocyte release without alteration of normal luteal function in rhesus monkeys.
BACKGROUND
Prostaglandins (PG), produced by the follicle just before ovulation, appear to act locally to promote follicle rupture and oocyte release.


METHODS
To determine whether administration of PG synthesis inhibitor directly into the primate follicle would prevent ovulatory events, serum estradiol was used to predict the day of the ovulatory LH surge in rhesus monkeys. On the day before or the day of the LH surge, vehicle (n = 9), the PG synthesis inhibitor indomethacin (10(-6) or 10(-5) mol/l final concentration; n = 8), or 10(-5) mol/l indomethacin + 1 micro g/ml PGE(2) (n = 3) was injected into the follicular fluid of the pre-ovulatory follicle. In some animals, luteal phase estrogen and progesterone were measured in daily serum samples. Other animals were ovariectomized 3 days after follicle injection; ovaries were examined for verification of follicle rupture and oocyte release.


RESULTS
Follicle injection of indomethacin [10(-6) mol/l (n = 4) or 10(-5) (n = 4) mol/l final concentration] or vehicle (n = 6) did not alter luteal function. Examination of serial sections of removed ovaries confirmed follicle rupture and the absence of oocytes in vehicle-injected follicles (n = 3). Trapped oocytes were observed in 4/8 indomethacin-injected follicles, though several ovaries with trapped oocytes had experienced follicle rupture. Oocytes were not detected in the ruptured, luteinizing follicles from indomethacin + PGE(2)-injected monkeys (n = 3).


CONCLUSIONS
Follicular administration of indomethacin can prevent oocyte release without inhibition of follicle rupture or disruption of subsequent luteal function. The ability of PGE(2) to prevent indomethacin-induced ovulatory failure suggests a critical role for locally produced PGE(2) in the process of oocyte release in primates.
Duffy
Diane M
DM
Division of Reproductive Sciences, Oregon National Primate Research Center, 505 NW 185th Avenue, Beaverton, OR 97006, USA. duffydm@evms.edu
Stouffer
Richard L
RL
D000818:Animals; D003338:Corpus Luteum / Q000187:drug effects* / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D015232:Dinoprostone / Q000008:administration & dosage*; D004338:Drug Combinations; D005260:Female; D006728:Hormones / Q000097:blood; D007213:Indomethacin / Q000008:administration & dosage*; D008253:Macaca mulatta; D009865:Oocytes / Q000166:cytology / Q000187:drug effects*; D006080:Ovarian Follicle / Q000187:drug effects*; D010053:Ovary / Q000166:cytology; D012016:Reference Values
D016861:Cyclooxygenase Inhibitors; D004338:Drug Combinations; D006728:Hormones; D015232:Dinoprostone; D007213:Indomethacin