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Theriogenology Jan 2017Effect of a GnRH-agonist (deslorelin) was studied on reproductive function and ovarian luteinizing hormone receptor (LHR) and follicle stimulating hormone receptor...
Effect of a GnRH-agonist (deslorelin) was studied on reproductive function and ovarian luteinizing hormone receptor (LHR) and follicle stimulating hormone receptor (FSHR) expression in prepubertal female cats that were either implanted with 4.7-mg deslorelin (implanted: n = 6) or not (controls: n = 18) or ovariohysterectomized at prepubertal age (prepubertal OVH: n = 6). Body weights, fecal estradiol, and sexual behavior of implanted and control cats were monitored for 48 weeks followed by collection of ovaries and uteri. Ovaries and uteri were collected from control cats at follicular, luteal, and inactive stage (n = 6/group) and from prepubertal OVH cats at prepubertal age. Ovaries and uteri were analyzed for anatomical/histological characteristics. Ovaries were also analyzed for LHR and FSHR expression. Statistical analysis showed higher (P ≤ 0.05) body weight in control than implanted cats only during 22nd to 26th weeks of the study. Estrus was observed in control cats only. Deslorelin reduced (P ≤ 0.05) ovarian weight and number of antral follicles but did not affect endometrial thickness and gland diameter. However, myometrial thickness of implanted cats was significantly lower than control cats at follicular and luteal stage. Ovarian LHR mRNA expression was lower (P ≤ 0.05) in implanted cats than control cats at follicular stage. FSHR mRNA and LHR protein expression did not differ among the three groups. FSHR protein expression was lower (P ≤ 0.05) in prepubertal OVH cats and was not affected by deslorelin. In conclusion, deslorelin suppresses reproductive function in prepubertal female cats for at least 48 weeks possibly through a change in the ovarian mRNA expression of LHR.
Topics: Animals; Cats; Drug Implants; Female; Gene Expression; Ovary; Receptors, FSH; Receptors, LH; Sexual Maturation; Triptorelin Pamoate
PubMed: 27743690
DOI: 10.1016/j.theriogenology.2016.09.003 -
Animals : An Open Access Journal From... Sep 2020Deslorelin implants have been used to produce a reversible sterilization in several species. In cats, the prolonged duration (12-15 months in tomcats and 18-22 months in...
Deslorelin implants have been used to produce a reversible sterilization in several species. In cats, the prolonged duration (12-15 months in tomcats and 18-22 months in queen) is often too much for cat breeders who request early implant removal. The interval between implant removal and resumption of reproductive function in cats has never been investigated. Eighteen tomcats received a 4.7 mg deslorelin implant placed in the periumbilical area and surgically removed during all seasons of the year after 3, 6, or 9 months (n = 6, 6, and 6 cats, respectively). Following implant removal, all cats received a clinical exam every two weeks, including testicular ultrasonographic measurement, observation of penile spikes, and blood collection for serum testosterone assay. Restoration of serum testosterone secretion occurred after 23 ± 6, 23 ± 6, and 22 ± 7 days in the 3-, 6-, and 9-month groups, respectively. Restoration of testicular function was confirmed by histology in 13/15 cats undergoing orchiectomy at the end of the study while the owners of the remaining two cats opted to maintain their animals intact. Removal of a 4.7 mg deslorelin implant after 3, 6, or 9 months is followed by resumption of serum testosterone secretion after about 3 weeks independent of age or season.
PubMed: 32887474
DOI: 10.3390/ani10091559 -
JFMS Open Reports 2023The aim of this clinical case presentation was to describe the effect of a 4.7 mg deslorelin implant placement in a pregnant queen during the second half of gestation,...
CASE SUMMARY
The aim of this clinical case presentation was to describe the effect of a 4.7 mg deslorelin implant placement in a pregnant queen during the second half of gestation, and the consequences of its removal on the pregnancy and parturition. A 5-year-old female cat exhibiting nesting behaviour and weight gain 10 days after placement of a deslorelin implant was presented for examination. Gestation was confirmed on ultrasound, with two well-formed kittens of a gestational age of approximately 7 weeks. The deslorelin implant placed on the umbilicus was removed 1 week later. No change in the pregnancy was observed after removal of the implant. The fetuses showed no signs of distress on ultrasound and radiography examination 4 days after removal of the implant. One week after implant removal, the queen naturally delivered two healthy kittens. The queen showed maternal behaviour with normal milk production.
RELEVANCE AND NOVEL INFORMATION
In the light of the lack of literature on implant injection and removal in the pregnant queen, this case report showcases a successful birth of healthy kittens without any subsequent adverse effect on the queen. Further study is needed to assess the safety of implant removal during pregnancy and potential use as a means to induce fertile oestrus in the queen.
PubMed: 37873522
DOI: 10.1177/20551169231201606 -
Animals : An Open Access Journal From... Sep 2022Although deslorelin slow-release implants are widely used in the clinic, detailed published information about the recovery of testosterone concentrations (T), semen...
Although deslorelin slow-release implants are widely used in the clinic, detailed published information about the recovery of testosterone concentrations (T), semen quality, and testicular and prostatic volume (TV, PV) after treatment is still missing. This article aims to characterize changes during restart after a five-months treatment and subsequent implant removal. Seven male Beagle dogs were treated with deslorelin (treatment group, TG), and three saline-treated dogs served as controls (CG). Deslorelin implants were removed after five months (D ex), followed by detailed andrological examinations for TV, PV, semen collection, and blood sampling for T-analysis with/without GnRH/hCG stimulation tests. TV, PV, and T increased rapidly after D ex in TG, not differing from CG from D91 (TV), D49 (PV), and D14 (T). The first sperm-containing ejaculates were collected between D49 and 70, whereas the samples were normospermic between D84 and 133. A T increase (>0.1 ng/mL) subsequent to the GnRH/hCG stimulation test was observed from D28/29 onwards, respectively. Histological assessment of testicular tissue at the end of the observational period (D149 after implant removal) revealed normal spermatogenesis. Our data confirm that the restart of endocrine and germinative testicular function is highly variable, but nevertheless, all of the effects induced were reversible.
PubMed: 36230286
DOI: 10.3390/ani12192545 -
Animals : An Open Access Journal From... Jan 2022Two prostanglandins (luprostiol, LUP, and dinoprost, DIN) and two ovulation-inducing agents (human Chorionic Gonadotropin, hCG, and deslorelin, DES) were evaluated for...
Two prostanglandins (luprostiol, LUP, and dinoprost, DIN) and two ovulation-inducing agents (human Chorionic Gonadotropin, hCG, and deslorelin, DES) were evaluated for luteolysis and estrus induction, and for ovulation induction, respectively, in embryo donor jennies. Twenty-six fertile Andalusian jennies were used. In Experiment 1, jennies ( = 112 cycles) were randomly treated with either LUP or DIN after embryo flushing. In Experiment 2, donors ( = 84 cycles) were randomly treated with either hCG or DES to induce ovulation. No differences were found between prostaglandins for all variables studied (prostaglandin-ovulation interval (POI), interovulatory interval (IOI), embryo recovery rate (ERR), positive flushing rate (PFR) and embryo grade (EG)). The ovulation rate was similar for hCG and DES (60.9% vs. 78.7%). However, the interval to ovulation (ITO) was affected (62.61 ± 7.20 vs. 48.79 ± 2.69 h). None of the other variables studied (ERR, PFR and EG) were affected ( > 0.05), except for embryo quality ( = 0.009). In short, both prostaglandins evaluated are adequate to induce luteolysis and estrus. Both ovulation-inducing agents hastened ovulation, but DES seems to be more effective than hCG. Follicular diameter affected the interval from treatment to ovulation, and high uterine edema was related to low embryo quality.
PubMed: 35049767
DOI: 10.3390/ani12020143 -
American Journal of Veterinary Research Jun 2017OBJECTIVE To evaluate effects of administration of a 4.7-mg deslorelin acetate implant on egg laying in healthy cockatiels (Nymphicus hollandicus). ANIMALS 52...
OBJECTIVE To evaluate effects of administration of a 4.7-mg deslorelin acetate implant on egg laying in healthy cockatiels (Nymphicus hollandicus). ANIMALS 52 cockatiels. PROCEDURES 26 breeding pairs (a female and its respective male in each pair) were selected on the basis of their history of egg laying. Female birds were sedated and received a 4.7-mg deslorelin acetate implant (n = 13) or placebo implant (13) in the subcutaneous tissues between the scapulae. Male and female birds of each breeding pair were placed in separate but adjacent cages. Birds were exposed to 16 hours of light and 8 hours of darkness. A nest box was placed in cages of female birds to stimulate reproductive activity. Egg production and quality were monitored daily for 365 days. RESULTS Deslorelin acetate implants significantly suppressed egg laying in cockatiels, compared with effects for the placebo implants. Eleven of 13 placeboimplanted birds laid eggs between 12 and 42 days after implantation. None of the deslorelin-implanted birds laid eggs within 180 days after implantation, and only 5 of 13 deslorelin-implanted birds laid an egg during the study period (first egg laid between 192 and 230 days after implantation). No differences in egg quality or number of eggs per clutch were observed between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE Insertion of a 4.7-mg deslorelin acetate implant suppressed egg laying in healthy cockatiels for at least 180 days. Studies are necessary to evaluate effects of a deslorelin acetate implant in other avian species or in association with reproductive disorders.
Topics: Animals; Breeding; Cockatoos; Drug Implants; Female; Male; Oviposition; Ovum; Reproduction; Triptorelin Pamoate
PubMed: 28541153
DOI: 10.2460/ajvr.78.6.745 -
British Journal of Pharmacology Jan 2016Drug-target residence time is an important, yet often overlooked, parameter in drug discovery. Multiple studies have proposed an increased residence time to be...
BACKGROUND AND PURPOSE
Drug-target residence time is an important, yet often overlooked, parameter in drug discovery. Multiple studies have proposed an increased residence time to be beneficial for improved drug efficacy and/or longer duration of action. Currently, there are many drugs on the market targeting the gonadotropin-releasing hormone (GnRH) receptor for the treatment of hormone-dependent diseases. Surprisingly, the kinetic receptor-binding parameters of these analogues have not yet been reported. Therefore, this project focused on determining the receptor-binding kinetics of 12 GnRH peptide agonists, including many marketed drugs.
EXPERIMENTAL APPROACH
A novel radioligand-binding competition association assay was developed and optimized for the human GnRH receptor with the use of a radiolabelled peptide agonist, [(125) I]-triptorelin. In addition to radioligand-binding studies, a homogeneous time-resolved FRET Tag-lite™ method was developed as an alternative assay for the same purpose.
KEY RESULTS
Two novel competition association assays were successfully developed and applied to determine the kinetic receptor-binding characteristics of 12 high-affinity GnRH peptide agonists. Results obtained from both methods were highly correlated. Interestingly, the binding kinetics of the peptide agonists were more divergent than their affinities with residence times ranging from 5.6 min (goserelin) to 125 min (deslorelin).
CONCLUSIONS AND IMPLICATIONS
Our research provides new insights by incorporating kinetic, next to equilibrium, binding parameters in current research and development that can potentially improve future drug discovery targeting the GnRH receptor.
Topics: Animals; Binding, Competitive; CHO Cells; Cricetulus; Fluorescent Dyes; Gonadotropin-Releasing Hormone; Humans; Iodine Radioisotopes; Kinetics; Radioligand Assay; Receptors, LHRH; Triptorelin Pamoate
PubMed: 26398856
DOI: 10.1111/bph.13342 -
Animals : An Open Access Journal From... Oct 2020This article presents the results of a randomized clinical trial, designed to compare the efficacy and therapeutic profiles of Ypozane (osaterone acetate-OA) or...
This article presents the results of a randomized clinical trial, designed to compare the efficacy and therapeutic profiles of Ypozane (osaterone acetate-OA) or Suprelorin (deslorelin acetate-DA) in male dogs with clinical signs of benign prostate hyperplasia (BPH). Forty-five intact male dogs were used in the study. The Group I (negative control) included 10 healthy dogs, the Group II (positive control) included 10 dogs with confirmed BPH and no treatment, whereas Group III and IV consisted of dogs with BPH and treated either with DA (15 dogs) or OA (10 dogs). The clinical response, testosterone and estradiol levels, hematology, biochemistry, and adverse effects incidence were evaluated. Both OA and DA proved to be effective for BPH treatment in dogs, as they allowed for the clinical remission in all treated dogs. The complete alleviation of BPH symptoms was noticed sooner with the use of OA (in 80% of dogs from day 7) compared to DA (in 40% of dogs within the first 21 days). The recurrence of clinical signs related to BPH was observed from week 24 in dogs treated with OA, whereas no relapse was noticed in dogs treated with DA at the end of the 36 weeks of the observation period. In 5 dogs (33%) treated with DA, a flare-up effect (increase in the clinical signs associated with BPH) was noticed on day 7. Despite individual differences in the clinical action, both medications were effective and safe options for the treatment of symptoms related to BPH in dogs.
PubMed: 33096806
DOI: 10.3390/ani10101936 -
Animal Reproduction Jan 2020Although equine blastocysts ≤ 300 µm in diameter can be successfully vitrified, larger equine blastocysts are not good candidates for cryopreservation. As Na,...
Although equine blastocysts ≤ 300 µm in diameter can be successfully vitrified, larger equine blastocysts are not good candidates for cryopreservation. As Na, K-ATPase is involved in maintaining blastocyst expansion, perhaps inhibition of this enzyme would be a viable method of reducing blastocyst diameter prior to cryopreservation. Objectives were to evaluate effects of ouabain-induced inhibition of Na, K-ATPase in equine blastocysts. Sixteen mares were ultrasonographically monitored, given deslorelin acetate to induce ovulation, and inseminated. Embryos (D7 and D9) were harvested and Na, K-ATPase inhibited for 1 or 6 h by exposure to 10 M ouabain, either natural ouabain or conjugated to fluorescein (OuabainFL), during incubation at 37° C. Evaluations included morphometric characteristics (bright field microscopy) and viability (Hoescht 33342 + propidium iodide). Blastocysts incubated for 6 h in Holding medium + ouabain (n=3) had, on average, a 45.7% reduction in diameter, with adverse morphologic features and no re-expansion after subsequent incubation in Holding medium for 12 h. In subsequent studies, even a 1-h exposure to Ouabain or OuabainFL, caused similar reductions, namely 38.7 ± 6.7% (n=5) and 33.6 ± 3.3% (n=7) for D7 and D9 blastocysts, respectively. Ouabain binding was confirmed after OuabainFL exposition and all embryos (n=12) lost viability. We concluded that Na, K-ATPase inhibition with ouabain caused death of equine blastocysts and therefore was not a viable method of reducing blastocyst size prior to cryopreservation.
PubMed: 32368275
DOI: 10.21451/1984-3143-AR2019-0079 -
Animals : An Open Access Journal From... Sep 2022Although registered since 2007, knowledge about changes in testosterone concentrations (T), testicular and prostatic volumes (TV, PV) and semen quality, as well as the...
Although registered since 2007, knowledge about changes in testosterone concentrations (T), testicular and prostatic volumes (TV, PV) and semen quality, as well as the time point of infertility following treatment with a 4.7 mg deslorelin (DES) slow-release implant, is limited. Therefore, seven sexually mature male dogs were treated with DES (TG); three male dogs treated with saline served as controls (CG). The study assessed local tolerance, TV, PV, semen parameters and T subsequent to GnRH/hCG stimulation in regular intervals. Local tolerance was good. In TG, T was increased right after treatment, but decreased four hours afterwards. Subsequently, TV, PV, semen quality and T decreased over time in TG, but not CG. T was basal (≤0.1 ng/mL) from D28 onwards. Response to GnRH/hCG stimulation was variable, with two TG dogs having increased T post-stimulation on all study days independent of pre-treatment concentrations. A(zoo)spermia in TG was observed from D35-D77 in all seven dogs. Whereas treatment was still effective in six TG dogs five months after implant insertion, it was fully reversed in one dog in terms of T and spermatozoa on the last examination. These results indicate high variation in individual dogs, necessary to consider when advising dog owners.
PubMed: 36139239
DOI: 10.3390/ani12182379