The Effects of a GnRH Antagonist, Cetrorelix, on Ovarian Function in Cattle

Estradiol-based ovulation synchronization protocol are effective for breeding management in cattle, however, political pressure from the European Union has resulted in many countries enacting similar bans on the use of estradiol in livestock animals. Our long-term goal is to engineer an alternative protocol for fixed-time artificial insemination that is simple, steroid-free, and effective during different stages of the estrus cycle. Two studies were conducted to determine the effects of a GnRH antagonist, cetrorelix, on the follicular dynamics in cattle during different stages of follicular growth and in different endocrine milieus. The specific objective was to test the hypothesis that cetrorelix would induce regression of the dominant follicle and induce a new follicular wave emergence at a predictable time after treatment. In the first study (Chapter 4, two experiments), we explored the effects of cetrorelix at three stages of dominant follicle development and synchrony of subsequent follicular wave emergence and ovulation in cattle. In this study, ovaries of sexually mature heifers (>13 months of age, n=8 per group) were examined daily by transrectal ultrasonography to detect ovulation (Day 0 = wave emergence) and record the number, location, and diameter of follicles. In Experiment 1 of Study 1, heifers were given two doses of cetrorelix (1.5mg x2; 0.5 mg/ml in 5% D-Mannitol) 24 hr apart im starting on Day 1 (Cetro1-2; early-growing/pre-selection phase dominant follicle), Day 3 (Cetro3-4; mid-growing phase dominant follicle), and Day 6 (Cetro6-7; static phase dominant follicle), or normal saline (Control). Jugular venipuncture plasma samples were collected 0, 2, 4, and 6 days after cetrorelix treatment to assess luteal function. In all cetrorelix-treated heifers, dominant follicle regression occurred, and a new follicular wave emerged consistently 5.8 ± 0.3 days after treatment. There was a tendency for cetrorelix to reduce the diameter of the corpus luteum (CL), but there was no difference in the luteal function or lifespan between Control and treatment groups. In Experiment 2 of Study 1, heifers were given a single bolus of 3 mg cetrorelix im on Day 1, 3, or 6 of the wave; prostaglandin 9 days after cetrorelix treatment; and then heifers were artificially inseminated 12 hr after estrus detection. A single bolus of cetrorelix induced similar follicular regression as in Experiment 1 and a new follicular wave emerged consistently 3.6 ± 0.3 days after treatment. Artificial inseminations resulted in a 56.5% pregnancy rate (n=13/23) in all cetrorelix-treated heifers versus 42.9% (n=3/7) in Control, indicating no adverse effects of cetrorelix on oocyte competence. In the second study (Chapter 5), we examined the effects of cetrorelix on the ability to induce a new follicular wave by inhibiting ovulation during the preovulatory phase (Experiment 1) and determined the effect of cetrorelix on the ovulatory ability of the dominant follicle to exogenous challenge of hCG (Experiment 2). In Experiment 1 of Study 2, heifers (n=6 per group) were given either a luteolytic dose of cloprostenol on Day 4 and 4.5 (PreOv group) or heifers were allowed to maintain a functional CL (Luteal group). All heifers were given 3 mg cetrorelix im on Day 5 and the ovaries were examined daily until the next ovulation or wave emergence. Cetrorelix prevented the dominant follicle from ovulating and induced follicular regression in the Luteal and PreOv groups, resulting in a consistent follicular wave emergence 3.1 ± 0.3 days after cetrorelix treatment. In Experiment 2 of Study 2, heifers were synchronized by ultrasound-guided follicular ablation in combination with an intravaginal progesterone-releasing device for 5 days and PGF at the time of removal. Heifers were given either cetrorelix (Cetro groups) or normal saline (Control groups) on Day 5 (2x2 factorial; n=6 heifers per group) and all groups were treated with 1500 IU of hCG im on Day 7. Jugular venipuncture plasma samples were collected from all animals for progesterone analysis (-24 hr, 24 hr, and 48 hr from cetrorelix treatment). Cetrorelix did not prevent the dominant follicle from ovulating in response to exogenous hCG 48 hr after treatment. Combined between the two experiments, cetrorelix does not affect the diameter, vascularity, and progesterone secretion of the CL. In summary, a single bolus or split doses of cetrorelix given during the pre-selection, growing, or static phase of dominant follicle development and during the preovulatory phase induced follicular regression, resulting in the emergence of a new follicular wave at a predictable interval post-treatment. CL function and subsequent oocyte competence were not affected. Finally, cetrorelix treatment is an effective method to synchronize wave emergence and ovulation for reproductive management in cattle.

Name thesis:degree_name

Master of Science (M.Sc.)

Level thesis:degree_level

Masters

Discipline thesis:degree_discipline

Veterinary Biomedical Sciences

Grantor

University of Saskatchewan

Year dc:date.issued

2024

Author dc:creator

• Farmer, Dylan R

Advisor dc:contributor.advisor

• Singh, Jaswant

Committee members dc:contributor.committeemember

• Adams, Gregg P
• Dadarwal, Dinesh
• Leonardi, Carlos EP
• Ferrari, Maud CO
• McCorkell, Rob

• cattle
• cetrorelix
• corpus luteum
• follicle dynamics
• GnRH antagonist
• ovarian function
• ovulation
• synchronization

Language dc:language.iso

en

Handle dc:identifier.uri

https://hdl.handle.net/10388/16227

OAI identifier oai:identifier

oai:harvest.usask.ca:10388/16227