title: Effects of a gonadotropin-releasing hormone analog on rabbit ovarian function.
abstract: This study was undertaken to elucidate the effects of a GnRH analog (GnRH-a) on rabbit ovulation, oocyte maturation, and steroidogenesis, and to verify whether treatment with a GnRH-a interferes with ovarian response to exogenous gonadotropin (hCG), both in vivo and in vitro. Three approaches were used. In the first, adult New Zealand White (NZW) rabbits were divided into two groups. Both received PMSG and hCG administered 72 h after PMSG. In the test group a GnRH-a, leuprolide acetate (LA; 20 microg/kg) was administered s.c. every 24 h. Treated rabbits showed a significant decrease in ovulatory efficiency (control = 88%; treated = 72%), and an increase in degeneration rate of preimplantation embryos (control = 30% vs. treated = 40%). For the second approach, in vitro perfusion experiments were designed to compare the direct effects of LA (10.000 ng/ml) and hCG (50 IU) on ovarian function and to verify whether the presence of a GnRH-a in the perfusate modifies the actions of hCG. 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 = 53%; hCG-treated LA-perfused = 31%; LA-perfused = 12%), and increased the degeneration 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 maturation, but increased oocyte degeneration rate. The potential for preimplantation 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 effects within the ovary.
authors.affiliation: Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: V
authors.initials: V
authors.lastname: Zanagnolo
authors.forename: A M
authors.initials: AM
authors.lastname: Dharmarajan
authors.forename: J
authors.initials: J
authors.lastname: Hesla
authors.forename: E E
authors.initials: EE
authors.lastname: Wallach
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D004958:Estradiol / Q000096:biosynthesis; D005260:Female; D005307:Fertilization in Vitro; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D016729:Leuprolide / Q000494:pharmacology*; D009865:Oocytes / Q000187:drug effects; D010053:Ovary / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010060:Ovulation / Q000187:drug effects; D010477:Perfusion; D011374:Progesterone / Q000096:biosynthesis; D011817:Rabbits
chemical_list: D006063:Chorionic Gonadotropin; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; D016729:Leuprolide