Cetrorelix suppresses the preovulatory LH surge and ovulation induced by ovulation-inducing factor (OIF) present in llama seminal plasma

Mauricio E Silva,Marcelo H Ratto,Ximena P Valderrama,Monserrat Guerra,Claudia Letelier,Gregg P Adams,Juan P Smulders

doi:10.1186/1477-7827-9-74

Abstract

BackgroundThe purpose of the study was to determine if the effect of llama OIF on LH secretion is mediated by stimulation of the hypothalamus or pituitary gland.MethodsUsing a 2-by-2 factorial design to examine the effects of OIF vs GnRH with or without a GnRH antagonist, llamas with a growing ovarian follicle greater than or equal to 8 mm were assigned randomly to four groups (n = 7 per group) and a) pre-treated with 1.5 mg of GnRH antagonist (cetrorelix acetate) followed by 1 mg of purified llama OIF, b) pre-treated with 1.5 mg of cetrorelix followed by 50 micrograms of GnRH, c) pre-treated with a placebo (2 ml of saline) followed by 1 mg of purified llama OIF or d) pre-treated with a placebo (2 ml of saline) followed by 50 micrograms of GnRH. Pre-treatment with cetrorelix or saline was given as a single slow intravenous dose 2 hours before intramuscular administration of either GnRH or OIF. Blood samples for LH measurement were taken every 15 minutes from 1.5 hours before to 8 hours after treatment. The ovaries were examined by ultrasonography to detect ovulation and CL formation. Blood samples for progesterone measurement were taken every-other-day from Day 0 (day of treatment) to Day 16.ResultsOvulation rate was not different (P = 0.89) between placebo+GnRH (86%) and placebo+OIF groups (100%); however, no ovulations were detected in llamas pre-treated with cetrorelix. Plasma LH concentrations surged (P < 0.01) after treatment in both placebo+OIF and placebo+GnRH groups, but not in the cetrorelix groups. Maximum plasma LH concentrations and CL diameter profiles did not differ between the placebo-treated groups, but plasma progesterone concentrations were higher (P < 0.05), on days 6, 8 and 12 after treatment, in the OIF- vs GnRH-treated group.ConclusionCetrorelix (GnRH antagonist) inhibited the preovulatory LH surge induced by OIF in llamas suggesting that LH secretion is modulated by a direct or indirect effect of OIF on GnRH neurons in the hypothalamus.

Highlights

The purpose of the study was to determine if the effect of llama ovulation-inducing factor (OIF) on LH secretion is mediated by stimulation of the hypothalamus or pituitary gland
Intramuscular administration of homologous seminal plasma [12,13,14] and purified llama OIF [15,16,17] resulted in a rapid increase in plasma LH concentration followed by ovulation [12,13,16,17], similar to that observed after mating [6,10,11]
No ovulations were detected in llamas pre-treated with cetrorelix, irrespective of subsequent treatment with gonadotropin-releasing hormone (GnRH) or llama OIF

Summary

Introduction

The purpose of the study was to determine if the effect of llama OIF on LH secretion is mediated by stimulation of the hypothalamus or pituitary gland. Later studies in llamas [6,10,11] revealed that ovulation is preceded by a sudden rise in plasma LH concentration beginning within 15 minutes of mating. Recent studies in llamas and alpacas [12,13,14,15,16,17] have demonstrated the presence of a potent ovulation-inducing factor (OIF) in the seminal plasma of these species, challenging the notion that physical stimulation from copulation is the only mating-related stimulus required to trigger ovulation. In a more recent study [16] llama OIF was identified as a 14 kDa protein, suggesting that this molecule may be part of a larger protein complex or be a bioactive form of a larger pro-hormone

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