Intravaginal administration of progesterone using a new technique for sustained drug release in goats.

The objective of the present study was to develop and evaluate a sustained release vaginal progesterone (P4) capsule containing a mixture of mucoadhesive polymer and silicone fluid. Goats were administered a gelatin capsule containing 0.4 g of P4 mixed in silicone fluid and either a hydroxypropylmethylcellulose (HM) or polyaclil starch (PA) base. The mean plasma P4 concentrations at 2 and 12 h after administration were significantly higher in goats treated with PA capsules than in those with HM capsules. The plasma P4 concentrations in goats treated with HM capsules increased and remained above 1.0 ng/ml for 96 h after administration, whereas the plasma P4 concentrations in goats treated with PA capsules remained above 1.0 ng/ml for only 24 h after administration. In the next experiment, an HM capsule was attached to a silicone device and inserted in the vagina for 10 days. The plasma P4 concentration remained similar to that of the natural luteal phase for 9 days. These results suggest that a mixture of mucoadhesive polymer and silicone fluid has the potential to be applied clinically as a sustained release base for estrus synchronization or hormonal therapy.

The efficacy of a newly developed neurokinin 3 receptor agonist B21-750 on luteinizing hormone secretion in cycling goats.

This study aimed to investigate the efficacy of a newly developed NK3 receptor agonist (B21-750) on the secretion of luteinizing hormone (LH) in association with ovarian steroid hormones during the follicular phase (FP, n = 5) and luteal phase (LP, n = 5) of Shiba goats. The FP group was treated with both prostaglandin F2α and progesterone-controlled internal drug release (CIDR) inserts for 10 d, and B21-750 (200 nmol) was injected 12 h after removing the CIDR. Meanwhile, the LP group received B21-750 injections on a day during the mid-luteal phase. LH secretion increased at 1 h after B21-750 injection in both groups. The percent changes in the area under the curve of LH was higher during the hour after injection than during the hour before injection in both groups. Thus, this study demonstrated that B21-750 induces rapid LH secretion for a short period during both the follicular and luteal phases.

Effect of repeated adrenocorticotropic hormone administration on reproductive function and hair cortisol concentration during the estrous cycle in goats.

Measurement of the cortisol concentration in hair has been used as an index of chronic stress in several species including humans, wildlife and domestic animals. However, how accurately the cortisol concentration in hair reflects the changes in circulating cortisol concentrations has not been well documented. The objective of the present study was to examine the effect of repeated adrenocorticotropic hormone (ACTH) administration on the reproductive function during the estrous cycle and hair cortisol concentrations in goats. In experiment 1, goats were administered ACTH (0.625 IU/10 kg of body weight, n = 6) or saline (n = 6) intramuscularly once a day for 7 days on Day 11-17 of the estrous cycle (day 0 was the day of ovulation). In experiment 2, goats were administered ACTH (0.625 IU/10 kg of body weight, n = 6) or saline (n = 6) intramuscularly twice a day on Day 11-24 of the estrous cycle. Blood samples were collected 0, 0.5, and 6 h after first administration to determine the circulating cortisol concentrations. Hair was clipped at 0, 1, and 2 months after the start of administration. In both experiments, the plasma cortisol concentration increased at 0.5 h and returned to baseline at 6 h after ACTH administration. During the experiments, estrus was observed in most animals in ACTH and saline groups (6/6 and 4/6 in experiment 1 and 5/6 and 6/6 in experiment 2, respectively) and ovulation was observed in all goats examined. However, the number of ovulatory follicles was significantly different between the ACTH and saline groups, and the maximal diameter of ovulatory follicles tended to be different (P = .07) between the ACTH and saline groups. In experiment 1, the hair cortisol concentration was not influenced by the ACTH administration throughout the sampling period. In experiment 2, the hair cortisol concentration in the ACTH group was greater at 1 month after administration than the pre-administration value, but was not significantly different at 2 months. These results suggest that repeated ACTH administration affects the development and ovulatory process of ovarian follicles and analysis of the hair cortisol concentration can be used for assessing relatively long-term changes in cortisol concentration in the circulation.

Effect of investigational kisspeptin/metastin analog, TAK-683, on luteinizing hormone secretion at different stages of the luteal phase in goats.

This study aimed to examine the response of luteinizing hormone (LH) secretion and ovarian steroid profile to TAK-683, an investigational metastin/kisspeptin analog, through treatment during different stages of the luteal phase in goats. Nine cycling Shiba goats (4.4 ± 2.3 years old) were assigned to early luteal phase (ELP, n = 4), mid-luteal phase (MLP, n = 4), and control (n = 5) groups. The ELP and MLP groups were administered 50 µg of TAK-683 intravenously on either day 5 or between days 7-14 after ovulation, respectively. The control group received vehicle between days 7-14 after ovulation. Blood samples were collected at 10-min (2-6 h), 2-h (6-24 h), and 24-h (24-96 h) intervals after treatment. Significant increases in plasma LH concentration were detected during the periods of 3 to 5 h and 2 to 5 h in the ELP and MLP groups, respectively. Estradiol concentrations continuously increased with the rise of basal LH secretion after TAK-683 treatment in two goats of the ELP group with a surge-like release of LH, but not in the goats without LH surge, i.e. the MLP and control group ones. Plasma progesterone concentration and the lengths of estrous cycle in all groups did not change significantly from the time before and after treatment. Present findings indicate that the responses of LH and ovarian steroids to treatment with TAK-683 depend on the stage of the luteal phase of the estrous cycle. We suggest that the stimulatory effects of TAK-683 on LH secretion are reduced in the process leading to the mid-luteal phase in cycling goats.

Video tracking analysis of behavioral patterns during estrus in goats.

Here, we report a new method for measuring behavioral patterns during estrus in goats based on video tracking analysis. Data were collected from cycling goats, which were in estrus (n = 8) or not in estrus (n = 8). An observation pen (2.5 m × 2.5 m) was set up in the corner of the female paddock with one side adjacent to a male paddock. The positions and movements of goats were tracked every 0.5 sec for 10 min by using a video tracking software, and the trajectory data were used for the analysis. There were no significant differences in the durations of standing and walking or the total length of movement. However, the number of approaches to a male and the duration of staying near the male were higher in goats in estrus than in goats not in estrus. The proposed evaluation method may be suitable for detailed monitoring of behavioral changes during estrus in goats.