No abstract

This study evaluated the effects of follicular phase administration of TAK-683, an investigational metastin/kisspeptin analog, on follicular growth, ovulation, luteal function and reproductive hormones in goats. After confirmation of ovulation by transrectal ultrasonography (Day 0), PGF2α (2 mg/head of dinoprost) was administered intramuscularly on Day 10 to induce luteal regression. At 12 h after PGF2α administration, intravenous administration of vehicle or 35 nmol (50 μg)/head of TAK-683 was performed in control (n = 4) and treatment (n = 4) groups, respectively. Blood samples were collected at 6-h intervals for 96 h and then daily until the detection of subsequent ovulation (second ovulation). After the second ovulation, ultrasound examinations and blood sampling were performed every other day or daily until the subsequent ovulation (third ovulation). Mean concentrations of LH and FSH in the treatment group were significantly higher 6 h after TAK-683 treatment than those in the control group (12.0 ± 10.7 vs 1.0 ± 0.7 ng/ml for LH, 47.5 ± 28.2 vs 15.1 ± 3.4 ng/ml for FSH, p < 0.05), whereas mean concentrations of oestradiol in the treatment group decreased immediately after treatment (p < 0.05) as compared with the control group. Ovulation tended to be delayed (n = 2) or occurred early (n = 1) in the treatment group as compared with the control group. For the second ovulation, ovulatory follicles in the treatment group were significantly smaller in maximal diameter than in the control group (3.8 ± 0.5 vs 5.4 ± 0.2 mm, p < 0.05, n = 3). Administration of TAK-683 in the follicular phase stimulates gonadotropin secretion and may have resulted in ovulation of premature follicles in goats.

The aim of the present study was to determine if the estradiol-induced luteinizing hormone (LH) surge is influenced by the constant exposure to TAK-683, an investigational metastin/kisspeptin analog, that had been established to depress the pulsatile gonadotropin-releasing hormone (GnRH) and LH secretion in goats. Ovariectomized goats subcutaneously received TAK-683 (TAK-683 group, n=6) or vehicle (control group, n=6) constantly via subcutaneous implantation of an osmotic pump. Five days after the start of the treatment, estradiol was infused intravenously in both groups to evaluate the effects on the LH surge. Blood samples were collected at 6-min intervals for 4 h prior to the initiation of either the TAK-683 treatment or the estradiol infusion, to determine the profiles of pulsatile LH secretion. They were also collected at 2-h intervals from –4 h to 32 h after the start of estradiol infusion for analysis of LH surges. The frequency and mean concentrations of LH pulses in the TAK-683 group were remarkably suppressed 5 days after the start of TAK-683 treatment compared with those of the control group (P<0.05). On the other hand, a clear LH surge was observed in all animals of both groups. There were no significant differences in the LH concentrations for surge peak and the peak time of the LH surge between the TAK-683 and control groups. These findings suggest that the effects of continuous exposure to kisspeptin or its analog on the mechanism(s) that regulates the pulsatile and surge mode secretion of GnRH/LH are different in goats.

Abstract. The aims of the present study were to investigate the profiles of ovarian steroids and luteinizing hormone (LH) and the appearance of estrous signs in relation to luteolysis and ovulation in lactating and non-lactating cows and to examine the influence of lactation on those observations. Five lactating (daily milk yield of 28.4 ± 3.2 kg; mean ± SD) and five nonlactating cycling Holstein cows were examined. Their ovaries were monitored by ultrasonography daily during one estrous cycle. Blood samples were collected daily and then at 3-h intervals after luteolysis until ovulation. Estrous signs in terms of behavior, the vulva and the vagina were checked at 8-h intervals after luteolysis until ovulation. Profiles of progesterone, estradiol-17β and LH did not differ between the groups. There were no differences in the interval from luteolysis to ovulation (4.6 ± 0.5 and 4.2 ± 0.8 days) and the interval from the estradiol-17β peak to ovulation (34.2 ± 4.5 and 30.6 ± 3.9 h) between lactating and non-lactating cows. The interval from the peak of the LH surge to ovulation was 27 h in all cows examined. Appearance of estrous signs did not differ between the groups. The vaginal estrous signs were observed conspicuously in all cows examined, but the behavioral signs were not observed in 20.0% of the cows. The duration of behavioral signs (41.3 ± 23.6 h) was shorter (P<0.05) than that of the vagina (68.9 ± 25.4 h). These results imply that lactation might not interfere with the hormonal profiles from luteolysis to ovulation.