EFFECTS OF A GONADOTROPIN-RELEASING-HORMONE ANALOG ON RABBIT OVARIAN-FUNCTION

This study was undertaken to elucidate the effects of a GnRH analog (G nRH-a) on rabbit ovulation, oocyte maturation, and steroidogenesis, an d to verify whether treatment with a GnRH-a interferes with ovarian re sponse to exogenous gonadotropin (hCG), both in vivo and in vitro. Thr ee approaches were used. In the first, adult New Zealand White (NZW) r abbits were divided into two groups. Both received PMSG and hCG admini stered 72 h aftel PMSG. In the test group a GnRH-a, leuprolide acetate (LA; 20 mu g/kg) was administered sc every 24 h. Treated rabbits show ed a significant decrease in ovulatory efficiency (control=88%; treate d=72%), and an increase in degeneration rate of preimplantation embryo s (control=30% vs. treated=40%). For the second approach, in vitro per fusion experiments were designed to compare the direct effects of LA ( 10.000 ng/ml) and hCG (50 IU) on ovarian function and to verify whethe r the presence of a GnRH-a in the perfusate modifies the actions of hC G. LA reduced the ovulatory efficiency of hCG-treated ovaries perfused in vitro (hCG-treated=87%; hCG-treated LA-perfused=70%), reduced the potential for preimplantation development (morula stage: hCG-treated=5 3%; hCG-treated LA-perfused=31%; LA-perfused=12%), and increased the d egeneration rate of early embryos (21%, 48%, and 56% respectively). In the third approach, the direct effect of LA (Group I: control, Group II:1.000 ng/ml, and Group III:10.000 ng/ml) on the in vitro maturation of denuded rabbit oocytes was evaluated. LA induced meiotic maturatio n, but increased oocyte degeneration rate. The potential for preimplan tation development was reduced (Morula stage: control=16%, Group II=8% , and Group III=6%), and degeneration rate was increased (38%, 65%, 63 % respectively). This study suggests that pharmacological doses of LA may exert a negative effect on oocyte function by direct action on the oocyte, indirectly via alteration of the intrafollicular environment and/or through interference with gonadotropin-induced biological effec ts within the ovary.