4 EFFECT OF A PROLONGED AROMATASE INHIBITOR TREATMENT ON PRE-OVULATORY OVARIAN FOLLICLES IN CATTLE

2012 ◽  
Vol 24 (1) ◽  
pp. 113 ◽  
Author(s):  
J. Yapura ◽  
J. Singh ◽  
R. J. Mapletoft ◽  
R. Pierson ◽  
D. Rogan ◽  
...  

Letrozole, a non-steroidal aromatase inhibitor, prevents the body from producing its own oestrogen. The potential use of this compound for herd synchronization is supported by previous studies in which letrozole treatment increased mean plasma LH concentrations, prolonged the period of dominance of the extant dominant follicle and delayed emergence of the next follicular wave. Heifers given a 3-day regimen of letrozole exhibited greater corpus luteum diameter indicative of a luteotrophic effect. The objective of the present study was to test the hypothesis that letrozole treatment during the development of the preovulatory follicular wave will delay ovulation. Post-pubertal beef heifers were given 2 luteolytic doses of PGF (12 h apart) and monitored by ultrasonography for ovulation. Ovarian follicular wave emergence was synchronized by ultrasound-guided transvaginal follicular ablation 5 to 8 days after PGF-induced ovulation (Day –1 = follicular ablation, Day 0 = wave emergence) and a luteolytic dose of PGF was given 60 and 72 h later. On Day 1, heifers were divided randomly into 2 groups (n = 15/group) and given an intravaginal device containing 1 g of letrozole or a blank device (control). The intravaginal devices were removed on Day 7, or at the time of ovulation, whichever occurred first. The ovaries were monitored by ultrasonography and a blood sample was collected daily from day of ablation to 12 days post-ovulation. Single point measurements were analysed by t-tests and serial data were analysed by analysis of variance for repeated measures. Multiple contrasts were made by Tukey's test. The interval from placement of the intravaginal device to ovulation was longer in letrozole-treated animals (6.1 ± 0.25 vs 5.1 ± 0.26 days, P < 0.01). Compared with controls, the day-to-day diameter profile of the dominant follicle of the ovulatory wave was larger (P < 0.05) and the maximum diameter greater (14.6 ± 0.51 vs 12.4 ± 0.53 mm; P < 0.01) in letrozole-treated heifers. The diameter profile of the corpus luteum formed post-letrozole treatment did not differ between groups; however, plasma P4 concentrations were higher (P < 0.01) in heifers treated with letrozole. In summary, a slow-release intravaginal letrozole device delayed ovulation by 24 h and induced the formation of a corpus luteum that secreted higher levels of progesterone. A slow-release intravaginal letrozole device may become useful for the development of an aromatase inhibitor-based protocol to control ovulation for herd synchronization and to enhance fertility by increasing circulating progesterone concentrations during the first 7 days post-AI or embryo transfer in cattle. Supported by the Natural Sciences and Engineering Research Council of Canada and Bioniche Life Sciences Inc.

2020 ◽  
Vol 32 (2) ◽  
pp. 204
Author(s):  
E. M. Zwiefelhofer ◽  
M. L. Zwiefelhofer ◽  
J. Singh ◽  
M. G. Colazo ◽  
G. A. Franco ◽  
...  

In a previous study involving the use of the aromatase inhibitor letrozole to synchronise ovulation, incomplete luteolysis appeared to confound the synchronising effect in letrozole-treated heifers. Experiments were done to determine whether letrozole treatment interferes with luteolysis and affects the timing of oestrus (Experiment 1) and whether pregnancy rate is affected by the stage of the oestrous cycle during which letrozole treatment is initiated (Experiment 2). In Experiment 1, Hereford heifers were fitted with a HeatWatch sensor and given prostaglandin F2α (PGF2α). Ovulation (Day 0) was determined by daily ultrasonography, and on Day 3 heifers were given an intravaginal letrozole-releasing device or a sham device for 4 days (n=16 per group). Half of the heifers in each group were given PGF2α on Day 7 (PGF 1×) or on Day 7 and 7.5 (PGF 2×). Ultrasonography and blood sampling were done daily from device insertion to removal, every 12h for 72h following PGF2α and daily for 14 days following ovulation. In Experiment 2, heifers were randomly assigned to three groups (n=10-11 per group) in which a 4-day letrozole-releasing device treatment was initiated during metoestrus (Days 0-2), diestrus (Days 7-9), or pro-oestrus (Days 15-17). Prostaglandin F2α was given at device removal and again 12h later. Heifers were inseminated with frozen-thawed semen and given gonadotrophin-releasing hormone 66h after device removal. Ultrasonography and blood sampling were done twice daily from device removal until ovulation. End points examined included dominant follicle and corpus luteum (CL) diameters, onset of oestrus, and plasma concentrations of oestradiol determined by radioimmunoassay. Nominal data were compared using GENMOD, analysis of variance, or mixed model for repeated-measures and were expressed as means±s.e.m. Proportional data were analysed using chi-square. In Experiment 1, no main effects or interactions were detected between device or PGF treatment for onset of oestrus following PGF2α (overall 60.0±2.5h) or CL diameter profiles during luteolysis. Residual variation was reduced in the timing of the first PGF to ovulation in the PGF 2× group versus the PGF 1× group (5.6±2.2h vs. 15.2±3.2 h; P&lt;0.01). The CL diameter following ovulation was greater in the PGF 2× group compared with the PGF 1× group (P=0.03). Circulating plasma oestradiol during treatment was greater (P=0.04) in both the PGF 1× and sham groups. In Experiment 2, a greater proportion of heifers in the pro-oestrus group ovulated ≤24h after device withdrawal compared with the metoestrus and diestrus groups combined (6/11 vs. 0/22, respectively; P&lt;0.05). Pregnancy rate tended to be greater in the metoestrus group than in the diestrus group (10/11 vs. 6/10; P=0.08), and pregnancy rate in both groups was greater than that in the pro-oestrus group (0/11; P&lt;0.05). In conclusion, letrozole treatment did not interfere with luteolysis, and PGF2α given 2× at a 12-h interval on Day 7 after ovulation decreased variance in the timing to ovulation. Treatment initiated during metoestrus and diestrus yielded greater pregnancy rates than that started during pro-oestrus and warrants efficacy testing in a large fixed-time AI field trial. This research was supported by Alberta Agriculture and Forestry and by Dechra.


2010 ◽  
Vol 22 (1) ◽  
pp. 271 ◽  
Author(s):  
M. J. Yapura ◽  
R. J. Mapletoft ◽  
J. Singh ◽  
R. A. Pierson ◽  
G. P. Adams

Many countries have banned the use of estrogenic products in farm animals. Nonsteroidal aromatase inhibitors prevent the body from producing its own estrogen. The effects on the ovary are thought to be a result of suppression of estrogen-producing follicles and a rebound in endogenous levels of FSH through the removal of the negative feedback effect of estradiol. An experiment was designed to determine the effects of a nonsteroidal aromatase inhibitor, letrozole, on ovarian function in cattle. The specific objective was to test the hypothesis that letrozole will arrest growth of the dominant follicle, resulting in emergence of a new follicular wave at a predictable interval post-treatment. Beef heifers were assigned randomly to 4 groups and given phosphate-buffered saline [control; (n = 10)] or letrozole at a dose of 500 (n = 9), 250 (n = 10), or 125 (n = 10) μgkg-1 i.v. 4 days after follicular ablation (≈ 2.5 days after wave emergence, at the time dominant follicle selection is manifest). Blood samples were collected and ovarian structures were monitored daily by transrectal ultrasonography. Analysis of variance for repeated measures, one-way ANOVA, paired t-test, and 2-sample t-test were applied to the analysis of the data. The diameter profile of the dominant follicle was larger in heifers treated with letrozole than in control heifers (P < 0.05). The intervals from treatment to new wave emergence and from treatment to onset of regression of the extant dominant follicle were longer (P < 0.05) in heifers treated with letrozole than in controls, although variances in the intervals were not different. A small but significant reduction in circulating estradiol concentration was observed, and plasma LH concentrations were higher (P < 0.05) in letrozole-treated heifers than in controls. Lower plasma concentrations of FSH in letrozole-treated heifers than in controls (P < 0.03) was interpreted as an indirect effect resulting from prolonged follicular dominance. In summary, a single dose of letrozole did not induce regression of the extant dominant follicle, nor did it directly affect FSH release. Conversely, letrozole extended the lifespan of the dominant follicle, in association with increased endogenous levels of LH, thereby delaying the next FSH surge and subsequent follicular wave emergence. Results suggest that letrozole has potential as a nonsteroidal method of controlling ovarian function in cattle but further studies are needed to clarify dosage and timing of treatment. Research supported by the Natural Sciences and Engineering Research Council of Canada and Bioniche Life Science Inc.


2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
R. I. Derar ◽  
H. A. Hussein

The objective of the current study was to describe follicular dynamics in Egyptian Jennies throughout the estrous cycle. In this experiment, 8 estrus cycles in 8 cyclic Jennies were studied from February to June using ultrasonography. The result revealed that one follicular wave per cycle was recorded throughout the studied period. Dominant follicle (DF) was firstly detected at day in Jennies. The growth rate of DF was  mm/day. Left ovulations were nonsignificantly () more than right ovulations (55.6% versus 44.6%). The CL was firstly detected at D , developed in a rate of  mm/day, reached a maximum diameter of  mm at D , and started to regress on D with a mean regression rate of  mm d-1. Results of the present study indicated that Jennies had one follicular wave per cycle. The Day of the cycle has a significant effect on the number of different classes of the ovarian follicles, but not large ones. Ultrasonographic characteristics of the preovulatory follicles could be useful to predict ovulation. CL developed and regressed in a slow rate.


Author(s):  
Vinny Dodiyar ◽  
Parkash Singh Brar ◽  
Narinder Singh ◽  
Mrigank Honparkhe

Background: Understanding of ovarian follicular dynamics and endocrine regulation is essential to design and use interventions to optimize reproductive efficiency. Bos indicus and Bos taurus cows have some differences in their follicular dynamics and ovarian steroidal hormones. The present study was planned to understand follicular dynamics vis-a-vis ovarian steroids profiles in Sahiwal cattle. Methods: The study was conducted in normal cyclic, pluriparous, non-lactating Sahiwal cows (n=7). Trans-rectal ultrasonography was performed to record the location, size, number of follicles and size of corpus luteum (CL) from the beginning, till the end of experiment. The dataset was used to characterize the follicular wave emergence, growth, regression, time of selection and ovulation of the dominant follicle in each cow. Result: Three Sahiwal cows showed two wave and four cows showed three wave estrous cycles with mean interovulatory length of 20.33±0.33 and 22.50±0.28 days, respectively. No significant difference was recorded in the maximum diameter of corpus luteum, P4 and E2 plasma levels between 2-wave and 3-wave estrous cycles. The peak progesterone values of 6.00±0.91 and 6.2±1.2 ng/ml and peak estradiol values of 15.83±0.60 and 14.31±0.44 ng/ml were recorded in 2-wave and 3-wave estrous cycle, respectively. The results showed that Sahiwal cows had 2-wave and 3-wave estrous cycle and the 3-wave estrous cycle had comparatively longer inter-ovulatory period and smaller maximum diameter of second wave dominant follicle than 2-wave estrous cycle.


2007 ◽  
Vol 19 (1) ◽  
pp. 242
Author(s):  
C. Kawashima ◽  
N. Sudo ◽  
C. Amaya Montoya ◽  
E. Kaneko ◽  
M. Matsui ◽  
...  

Recent studies have shown that IGF-1 is a crucial factor for ovarian follicular development in mammals. In postpartum (pp) dairy cows, plasma IGF-1 and estradiol (E2) levels in ovulatory cows at the first follicular wave pp are higher than in anovulatory cows. However, the plasma IGF-1 profile in an ovulatory or anovulatory dominant follicle (DF), which have different E2 production, at the first follicular wave pp have not yet been elucidated. Thus, we investigated the changing profile of plasma IGF-1 levels during first follicular wave pp. In 22 multiparous Holstein cows, blood samples were obtained 2 times/week from 4 weeks prepartum to 3 weeks pp, and the first follicular wave was monitored by ultrasound 2 times/week from 7 days pp to ovulatory phase. Detailed IGF-1 profiles in blood were determined during DF growth and maturation 4 times/day from 10 days pp to 7 days after the first ovulation in 5 ovulatory cows and to 20 days pp in 4 anovulatory cows; the data were analyzed by repeated measures ANOVA, and Student&apos;s t-test. There was no interaction between groups and time within the prepartum or the pp period. The ovulatory cows (n = 13/22) with an estrogen-active dominant (EAD: high plasma E2 level with peak) follicle showed higher IGF-1 levels than anovulatory cows (n = 9/22) with an estrogen-inactive dominant (EID: low plasma E2 level without peak) follicle during the prepartum (117 � 8 vs. 91 � 5 ng mL-1; P &lt; 0.05) and the pp (91 � 4 vs. 64 � 4 ng mL-1; P &lt; 0.001) period. Especially noteworthy, during the first follicular wave pp in ovulatory cows, the plasma IGF-1 levels were maintained at a high level until E2 levels increased, followed by an LH surge. We observed that the EAD follicle in ovulatory cows ovulated. To further examine the IGF-1 system in the intra-follicular environment, we used the EAD and EID follicles from ovaries of dairy cows obtained at a slaughterhouse. The EAD and EID follicles were classified on the basis of follicle diameter and E2 concentrations in follicular fluid (FF). The significant differences of factors between EAD and EID were analyzed by Student&apos;s t-test. The expression of IGF-1 mRNA was not detected in follicular cells in either EAD and EID, suggesting that IGF-1 in FF is mainly derived from liver. The free IGF-1 levels in FF in EAD (4.8 � 0.5 ng mL-1) were higher than those in EID (2.7 � 0.1 ng mL-1; P &lt; 0.05). In addition, the expression of type 1 IGF receptor (IGFR-1) mRNA in EAD was higher than hat in EID (P &lt; 0.0001). From the results of the present study, it is apparent that the EAD follicle during the first follicular wave pp in ovulatory cows sufficiently expressed IGFR-1, and a liver-derived IGF-1 stimulates E2 production in the follicle to ovulate. In conclusion, our data suggest that a high concentration of IGF-1, secreted from the liver, during the peripartum period may be one of important factors for the appearance of an ovulatory follicle during the first follicular wave pp cows.


1993 ◽  
Vol 73 (2) ◽  
pp. 267-275 ◽  
Author(s):  
G. P. Adams ◽  
K. Kot ◽  
C. A. Smith ◽  
O. J. Ginther

The relationship between a dominant follicle of a follicular wave and the suppression of subordinate follicles was studied during the first postovulatory wave (Wave 1) in Holstein heifers. The dominant follicle (largest follicle) was cauterized or a sham-operation was done on day 3 (day 0 = ovulation) using seven heifers per group. In the cautery group, compared to the controls, the largest subordinate follicle attained a larger diameter (11 7 vs 8 0 mm; P < 0.01), reached maximum diameter at a later day (day 9.2 vs. day 3.1; P < 0 01) and began to regress at a later day (day 14.3 vs. day 5.7; P < 0.01). In addition, the emergence of Wave 2 was hastened (day 6.4 vs. day 9.3; P < 0.05) and more heifers had more than two waves per interovulatory interval (5 of 6 vs. 2 of 7; P < 0.05). In heifers with the dominant follicle eliminated, the largest subordinate grew to the diameter of a dominant follicle during Wave 1 (n = 3) or became the dominant follicle of a newly emerged wave (n = 2). A subordinate sometimes persisted as a small follicle (e.g., 5 mm) for several days before resurging. However, it was not convincingly demonstrated that a subordinate follicle could resurge after it had begun to regress (decrease in diameter). Results supported the hypothesis that suppression of subordinate follicles is a prolonged process, so that resurgence of a subordinate can occur if the dominant follicle is removed. Key words: Ovaries, follicular waves, selection, cattle, cauterization


2012 ◽  
Vol 24 (4) ◽  
pp. 631 ◽  
Author(s):  
M. Jimena Yapura ◽  
Reuben J. Mapletoft ◽  
Jaswant Singh ◽  
Roger Pierson ◽  
Jonathan Naile ◽  
...  

Effects of the non-steroidal aromatase inhibitor letrozole on ovarian function in cattle were determined. The hypothesis that letrozole would arrest growth of the dominant follicle, resulting in emergence of a new follicular wave at a predictable post-treatment interval, was tested. Heifers were assigned randomly to four groups 4 days after follicular ablation (~2½ days after wave emergence) and given intravenous doses of 500 (n = 9), 250 (n = 10), or 125 µg kg–1 (n = 10) letrozole or phosphate-buffered saline (controls; n = 10). Blood was collected and ovarian structures were monitored daily by transrectal ultrasonography. Plasma concentrations of LH and FSH were measured by radioimmunoassay; plasma concentrations of letrozole were determined by high-performance liquid chromatography tandem mass spectrometry. A single intravenous dose of letrozole did not induce regression of the dominant follicle present at the time of treatment, nor did it directly affect FSH release. Conversely, treatment with letrozole increased endogenous concentrations of LH and extended the lifespan of the dominant follicle, which delayed the next FSH surge and subsequent follicular wave emergence. Letrozole continues to have potential as a non-steroidal treatment for controlling ovarian function in cattle.


2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 377-377
Author(s):  
Giovanni M Baez ◽  
Wilfran E Rivera

Abstract Tropical cow-calf operations using Bos indicus crossbreds are characterized by extended periods of time before the establishment of ovarian cyclicity. The aim was to determine whether the increase of progesterone concentrations during postpartum anestrous using intravaginal devices along with injection of estradiol benzoate would advance the occurrence of first ovulation after calving. 269 suckled crossbred cows kept in different farms at North-Santander (Colombia) were randomized in one of the following treatments: 1:Control (n = 88) no further treatment; 2:P4 (n = 91) cows received an intravaginal device containing 0.588 g of progesterone during 7 days at day 50±3 after calving; 3:P4+E2 (n = 90) as treatment 2 plus an additional injection of 2.0 mg of estradiol benzoate at the time of device insertion. Ovarian ultrasound was performed weekly starting on the day of treatments until ovulation (disappearance of a dominant follicle with later appearance of a corpus luteum within two consecutive examinations). Calving-Ovulation Interval was recorded and means between groups were analyzed using ANOVA (α=0.05). For the control group, COI tended (P = 0.08) to be longer for primiparous cows (149.6±4.5 days, n = 14) compared to multiparous cows (140.4±2.1d, n = 74). Treatment with P4 reduced the COI for both primiparous (105.3±5.4d, n = 15; P &lt; 0.0001) and multiparous (96.4±3.0d, n = 76; P &lt; 0.0001) compared to the controls (P = 0.21 between groups of age). When primiparous cows were treated with P4+E2 the COI decreased compared to both P4 and control treatments (82.3±2.8d, n = 17; P &lt; 0.0001). However, in multiparous cows there was no effect of P4+E2 compared to P4 treatment (94.6±2.6d, n = 73; P = 0.65), then COI was shorter for primiparous compared to multiparous cows (P = 0.03) with P4+E2 treatment. The use of an intravaginal device containing progesterone advances the time of first ovulation after calving in suckled cows. Additional use of estradiol benzoate reduces the time for first ovulation in primiparous but not multiparous cows.


2004 ◽  
Vol 16 (2) ◽  
pp. 233
Author(s):  
R.S. Jaiswal ◽  
J. Singh ◽  
G.P. Adams

Knowledge about the developmental pattern of small follicles (&lt;4mm) will be crucial to understanding the endogenous control of folliculogenesis and to developing methods to control it for clinical purposes. This study was designed to characterize the developmental pattern of 1–3mm follicles and to determine, retrospectively, the stage at which the future dominant follicle first attains a size advantage among follicles in the cohort. In Experiment 1, the ovaries of Hereford-cross heifers (n=18) were examined daily by high resolution transrectal ultrasonography for one natural interovulatory interval to evaluate changes in the number of 1–3-mm follicles in relation to the wave pattern of follicles ≥4mm. Interovulatory interval was divided into 2- and 3-wave based on number of waves exhibited by heifers. In Experiment 2, the ovaries of Hereford-cross cows (n=9) were examined every 6h from Day 5 to Day 13 (Day 0=ovulation) to monitor precisely the diameter changes of individual follicles ≥1mm during emergence of the second follicular wave. Data were analyzed by Proc. Mixed procedure for repeated measures (Littell RC et al., 2000 Stat in med 19, 1793–1819) in the Statistical Analysis System software package (SAS version 8.2 for MS Windows;; 2002 SAS Institute Inc. Cary, NC, USA). Results of Experiment 1 revealed a day effect (P&lt;0.05) on the number of small (1–3mm) follicles, with a peak (P&lt;0.05) 1 or 2 days before wave emergence (defined as the day the dominant follicle was first detected at 4mm), followed 3 to 4 days later by a peak (P&lt;0.05) in the number of large follicles (≥4mm). There was an inverse relationship between the number of small and large follicles during Wave 1 (r=−0.66; P=0.05) and Wave 2 (r=−0.62; P=0.04) in 2-wave interovulatory intervals. Similarly, an inverse relation was detected between the number of small and large follicles for Wave 1 (r=−0.79; P=0.01) and Wave 3 (r=−0.90; P&lt;0.01) but not for Wave 2 (r=−0.57; P=0.14) in 3-wave interovulatory intervals. The number of 1–3-mm follicles detected in anovulatory waves did not differ (P=0.53) between 2- versus 3-wave interovulatory intervals;; however, a difference (P&lt;0.05) was observed between anovulatory and ovulatory waves in 3-wave interovulatory intervals but not (P=0.63) in 2-wave interovulatory intervals. Experiment 2 permitted the identification of the future dominant follicle at a diameter of 1mm and its emergence at 6–12h earlier than the largest subordinate follicle (P&lt;0.01). Emergence of the future dominant (r=0.71; P=0.05) and 1st subordinate (r=0.78; P=0.02) follicles was temporally associated with a wave-eliciting rise in circulating concentrations of FSH. Growth rate of the dominant and the 1st subordinate follicle differed (P&lt;0.01) from 2nd subordinate follicle at 84h after their detection at 1mm. It was concluded that small antral follicles (1–3mm) develop in a wave-like manner, and apparent selection of the dominant follicle was manifest much earlier than previously documented.


Sign in / Sign up

Export Citation Format

Share Document