The Effects of a GnRH Antagonist, Cetrorelix, on Ovarian Function in Cattle
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".