Delay of Ovulation Due to Diets Containing Levonorgestrel in Cynomolgus Monkeys (<i>Macaca fascicularis</i>)

Abstract

ABSTRACT. This study was undertaken to develop a simple and practical method to control the time of ovulation in cynomolgus monkeys. Diets containing a synthetic gestagen, levonorgestrel (LNG) were given daily to normally cycling female monkeys for 2 weeks, and plasma concentrations of estradiol-17β and progesterone were determined by EIA in order to estimate the time of ovulation. Doses of LNG (0, 3.2,8, 20, 50, or 125 µg) were given from Day 2 (Day 0 =the first day of menstruation) through Day 15. The numbers of days from the last administration of LNG to the estimated ovulation in the groups treated with LNG at 20 µg and above were significantly greater than those in the controls, and the values in the group treated with LNG at 50 µg were within a narrow range. In a second experiment, LNG was administered at 50 µg in different phases of the menstrual cycle (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36), and the results indicated that ovulation occurred more than 12 days after the last administration in all monkeys, and the number of days from the last administration of LNG to the estimated ovulation in the group treated on Days 16-29 (luteal phase) was significantly greater than that in the group treated on Days 23-36. These results indicate that daily provision of a diet containing 50 µg LNG could be applicable for delaying ovulation, and suggest that the total level of (exogenous and endogenous) progestins is critical for determining the length of ovulation delay in cynomolgus monkeys. KEY WORDS: control of ovulation time, levonorgestrel, monkey.doi: 10.1292/jvms.12-0023; J. Vet. Med. Sci. 74(11): 1453-1460, 2012 Monkeys, whose physiological characteristics are close to those of humans, are indispensable experimental animals. In particular, recent safety research using monkeys has contributed to the development of new drugs. Although there is much demand for monkeys as experimental animals, their reproductive efficiency is generally very low.Although estrous cycle manipulation has been used as a research and management tool for studying and maximizing reproductive performance in domestic livestock species [1,2,7], there is little information about control of the ovarian cycle in monkeys. Menstrual cycle synchronization was attempted by orally administering a progestin, altrenogest, to 4 rhesus monkeys and the possibility of achieving ovulation synchronization was suggested [8]. Daily intramuscular injection with a commonly used progestin contraceptive, levonorgestrel (LNG), inhibited follicular maturation and ovulation in cynomolgus monkeys [6]. A single subcutaneous administration of a synthetic progestogen, danazol, induced a prolonged suppression of ovarian cyclicity in cynomolgus monkeys [3]. Although these findings suggest that the use of progestogens is effective for control of ovulation in monkeys, suitable doses and effects of the treatment at different phases during the menstrual cycle had not been studied.This study was performed ...

Development of a new device for artificial insemination in cynomolgus macaques

“…In Experiment 2, to determine whether this AI method can lead to pregnancy, AI was performed once on each of 10 females that were at pre-ovulation as determined by observing the dominant follicle using laparoscopy. Females treated with 50 µg/head/day levonorgestrel (D(-)-Norgestrel, Sigma-Aldrich, St. Louis, MO, USA) for 14 days to synchronize their menstrual cycles, as described previously [16], were subjected to AI using the newly developed device. Levonorgestrel inhibits follicular maturation and ovulation in cynomolgus macaques at different phases of the menstrual cycle, and the menstrual cycle restarts upon withdrawing levonorgestrel administration.…”