Effect of Testosterone on Ovarian Function in Beef Heifers
Synchronization of follicular wave emergence forms the basis of many reproductive management techniques used in the cattle industry such as estrus synchronization, fixed-time artificial insemination and embryo transfer. Estrogen in combination with progesterone has been used widely for this purpose due to ease of use and efficient, consistent and quick results, irrespective of the status of the dominant follicle or corpus luteum when the treatment is applied. The recent ban by the European Union on use of estrogens in food-producing animals prompted us to examine if testosterone could be used as an alternative drug for follicular wave synchronization. We tested the hypothesis that the administration of testosterone will shorten the life-span of the extant dominant follicle resulting in early emergence of a new follicular wave. We tested two forms of testosterone (conjugated form: testosterone enanthate and unconjugated form: non-esterified free testosterone) and determined that intramuscular injection of oil-based preparation of the unconjugated form caused a sharp rise in plasma concentrations of testosterone followed by a less rapid decline. The pharmacokinetics of testosterone in blood plasma of 16 heifers was determined after two intramuscular injections of 200 mg of unconjugated testosterone (in 4 ml canola oil) at 12 hour intervals. Testosterone C max was 13.9 ng/mL and the distribution half-life of testosterone in the bloodstream was 3.2 days. Plasma testosterone concentrations were elevated within 2 hours, maintained for initial 36 hours and declined to baseline over 13 days. To study the ovarian and endocrine effects of testosterone, heifers (n=6 per group) were given two intramuscular injections of 200 mg of unconjugated testosterone in 4 mL canola oil at 12 hour intervals on Days 1 (T1), 3 (T3) or 6 (T6) of the first follicular wave (Day 0 = ovulation); the Control group was given 4 mL canola oil. Ovarian structures were monitored daily by transrectal ultrasonography over one interovulatory interval and plasma samples were collected. Following treatment, the dominant follicle grew more slowly for the next 5 days in T1 (P=0.05) and T3 (P=0.06) groups compared to the Control group, while the dominant follicle in the T6 group regressed more slowly (P=0.02) than in the Control group. The diameter profile of the dominant follicle of the post-treatment wave (Wave 2) and the ovulatory wave did not differ between treatment and Control groups. Overall, testosterone treatment (T1, T3 and T6 combined) extended the duration of current (Wave 1; P=<0.001) wave in 8 out of 17 heifers compared with the Control group and emergence of the post-treatment wave was not synchronized. Although the interovulatory interval was not affected by the treatments, the proportion of 2-wave cycles tended to be higher (P=0.08) after treatment (T1, T3 and T6 combined) compared to the Control group. The plasma LH concentrations in T1 and T3 groups decreased after treatment, while it did not change in T6 group compared to Control group. FSH concentrations were not affected by the testosterone treatment. In conclusion, our hypothesis that exogenous testosterone treatment will hasten the emergence of next follicular wave, was not supported. Furthermore, testosterone treatment did not cause the demise of the dominant follicle. Testosterone treatment resulted in slower growth of the dominant follicle when treatment was initiated at or before the time of dominant follicle selection, and slower regression of the dominant follicle when treatment was initiated during the static phase. These changes appear to be mediated by the decline in systemic concentration of LH. In addition, testosterone treatment delayed the emergence of the next follicular wave irrespective of the status of the dominant follicle at the time of treatment.
Testosterone, follicle development, cattle, corpus luteum, ultrasonography, follicular and luteal dynamics, FSH, LH, Pharmacokinetics
Master of Science (M.Sc.)
Western College of Veterinary Medicine
Veterinary Biomedical Sciences