Acute depletion of murine primordial follicle reserve by gonadotropin-releasing hormone antagonists.
OBJECTIVE
To examine the effects of GnRH antagonists on preantral follicle survival in vivo and to investigate whether GnRH antagonist use during cyclophosphamide treatment would protect the ovary and preserve primordial follicle survival in a murine model.


METHODS
Prospective basic research study.


METHODS
Research laboratory in an academic medical center.


METHODS
Adult C57Bl/6 mice (5 to 6 weeks old).


METHODS
Mice received either a single injection of GnRH agonist (leuprolide acetate) on study day -10 or injections of the GnRH antagonist (antide or cetrorelix) on study days -3 and 0. Some animals also received the chemotherapeutic agent cyclophosphamide on day 0. All animals were killed by CO2 asphyxiation on day 7. To examine direct vs. indirect effects, some mice received GnRH antagonist under the bursa of one ovary, with the contralateral ovary receiving vehicle. Ovaries were fixed in Kahle's solution; 7-mum tissue sections were stained with Lillie's allochrome, and preantral follicles were counted on every fifth section.


METHODS
Numbers of primordial, primary, and secondary follicles.


RESULTS
Systemic administration of both GnRH antagonists caused a significant destruction of primordial follicles compared with control mice. Similar results were obtained whether the antagonists were administered systemically or directly to the ovary. Gonadotropin-releasing hormone agonist had no effect on primordial follicle numbers by itself but reduced the follicular depletion caused by cyclophosphamide.


CONCLUSIONS
In contrast to the effects of GnRH agonists to reduce chemotherapeutic destruction of primordial follicles, GnRH antagonists do not protect the ovary from the damaging effects of cyclophosphamide. More importantly, GnRH antagonists alone deplete primordial follicles in this murine model, likely through a direct effect on the ovary. Whether these observations apply to other species requires further study.
Danforth
Douglas R
DR
Department of Obstetrics and Gynecology, The Ohio State University, Columbus, Ohio 43210, USA. danforth.2@osu.edu
Arbogast
Laura K
LK
Friedman
Chad I
CI
D000818:Animals; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000502:physiology; D006727:Hormone Antagonists / Q000494:pharmacology*; D016729:Leuprolide / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000494:pharmacology; D006080:Ovarian Follicle / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology
D006727:Hormone Antagonists; D009842:Oligopeptides; D007987:Gonadotropin-Releasing Hormone; C057022:iturelix; D016729:Leuprolide