Steroid reduction during ovarian stimulation impairs oocyte fertilization, but not folliculogenesis, in rhesus monkeys.
OBJECTIVE
To test the hypothesis that steroids locally modulate and may be required for normal follicular function and gametogenesis in primates, the effects of steroid reduction during gonadotropin-stimulated folliculogenesis was studied in rhesus monkeys.


METHODS
Animals received human FSH (hFSH; days 1 to 6) and hFSH+human LH (hLH; day 7) to promote multiple follicular growth, and then received hCG (day 8) for ovulatory maturation. Four animals received trilostane (3 beta-hydroxysteroid dehydrogenase inhibitor) on days 1 to 8 or no inhibitor (controls; n = 4). Follicles were aspirated 34 hours after hCG.


METHODS
Follicular growth, serum E2, P, and pregnenolone, oocyte nuclear maturity, and IVF.


RESULTS
Trilostane markedly reduced E2 to levels as low as 7% of controls throughout the follicular phase. Pregnenolone was 66-fold greater during trilostane treatment relative to controls. In both groups, P was at baseline during follicular stimulation but was reduced for 72 hours after hCG in trilostane-treated animals. Despite E2 suppression, follicular growth and oocyte nuclear maturity were unaltered by trilostane. Trilostane hindered the fertilizability of metaphase II oocytes (15%) in three of four animals compared with controls (65%). Metaphase I oocytes that required > 8 hours to complete meiosis in vitro failed to fertilize in the same three of four receiving trilostane relative to controls (31%).


CONCLUSIONS
Follicular growth and oocyte meiosis did not require high or increasing E2 levels. Levels of follicular products other than E2 may be of value in determining the progress of ovarian stimulation protocols. However, the acquisition of oocyte competence for fertilization may require steroids.
Zelinski-Wooten
M B
MB
Division of Reproductive Sciences, Oregon Regional Primate Research Center 97006.
Hess
D L
DL
Wolf
D P
DP
Stouffer
R L
RL
D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D004958:Estradiol / Q000097:blood; D005260:Female; D005307:Fertilization in Vitro; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D006062:Gonadotropins / Q000494:pharmacology*; D008183:Luteal Phase / Q000502:physiology; D007986:Luteinizing Hormone / Q000494:pharmacology; D008253:Macaca mulatta; D008297:Male; D009865:Oocytes / Q000166:cytology / Q000502:physiology; D009866:Oogenesis / Q000502:physiology*; D006080:Ovarian Follicle / Q000502:physiology*; D010053:Ovary / Q000187:drug effects / Q000502:physiology*; D010062:Ovulation Induction; D011374:Progesterone / Q000097:blood; D013084:Sperm-Ovum Interactions / Q000187:drug effects / Q000502:physiology*
D006063:Chorionic Gonadotropin; D006062:Gonadotropins; D013196:Dihydrotestosterone; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D015096:3-Hydroxysteroid Dehydrogenases; C009954:trilostane