lecirelin and Follicular-Cyst

Bovine follicular cysts are an ovarian disorder of dairy cows associated with abnormal estrous behaviour and infertility. The treatment of choice is intramuscular administration of a GnRH analogue, which acts by triggering pituitary release of LH. However, the presence of GnRH and GnRH receptors on spinal cord and ovary in some species, and the kind of innervation of the ovary, let us hypothesize that GnRH and its analogues may also act when administered by epidural route, as happens for other drugs. Therefore the aim of this study was to compare the effects of epidural vs intramuscular administration of lecirelin (a GnRH analogue) on FC regression, estrus detection and pregnancy outcomes. The study was conducted on 220 Friesian cows affected by follicular cysts, divided among 4 groups: Group L(epid) and Group L(im) received, respectively 50 μg of lecirelin in the epidural space and intramuscular; Group C(epid) and Group C(im) were used as control groups. In Group L(epid), estrus induction and pregnancy rates were significantly higher than in Group L(im). The results of this study show that the epidural administration of lecirelin promoted the remission of follicular cysts and an improvement of reproductive parameters compared to intramuscular administration. Thus, an alternative therapeutical approach is available for FC treatment, in order to obtain an easier restoration of the ovarian activity, especially in those cases refractory to classical therapeutic approaches.

Topics: Animals; Cattle; Cattle Diseases; Female; Follicular Cyst; Injections, Epidural; Injections, Intramuscular; Oligopeptides

Bovine follicular cysts (FCs) are a common cause of economic loss in modern dairy herds. Their aetiopathogenesis is not completely understood, even though an inadequate hypothalamic release of GnRH at the time of ovulation is considered to be their main cause. Much evidence, however, suggests a role for adrenergic innervation in ovarian functions, such as follicular development, steroid hormone secretion, and follicular contractility, the latter being an event important for ovulation. Moreover, in humans, polycystic ovary syndrome, a disease very similar to bovine follicular cysts, is characterised by increased density of adrenergic nerves. Given these premises, the aim of our study was to evaluate the effectiveness and mode of action of a novel strategy for the treatment of bovine follicular cysts. In the in vivo experiment, 170 Friesian cows diagnosed with follicular cysts were assigned to four groups (groups A, B, C, and D) to assess the effects of epidural administration of a β-adrenergic antagonist (carazolol) alone or in combination with a GnRH analogue (lecirelin). The four groups underwent the following treatments: Group A was administered lecirelin in combination with carazolol; Group B was administered carazolol; Group C was administered lecirelin; and Group D was administered only normal saline solution. In the in vitro experiment, strips of the walls of cystic follicles recovered post-mortem were suspended in an organ bath, connected to an isometric force transducer and exposed to increasing doses of epinephrine or to the same treatment after exposure to carazolol for 15 min (n = 10). The amplitude and frequency of the contractile activity were recorded. None of the control cows was observed in oestrus or was submitted to AI. The combination of lecirelin and carazolol induced a significant increase in the number of cows in oestrus (88%) compared to lecirelin alone or to carazolol alone (P < 0.05 and P < 0.01, respectively). The combination of lecirelin and carazolol and lecirelin alone were significantly more efficacious than carazolol alone (P < 0.01 and P < 0.05, respectively). In the in vitro experiment, epinephrine increased the amplitude of the contractions of the strips in a dose-dependent manner. This response was significantly enhanced in strips pre-treated with carazolol. The treatments had no effect on the frequency of contractions. In conclusion, our work demonstrates that the epidural administration of a GnRH analogue and a β-adren

Topics: Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Animals; Cattle; Cattle Diseases; Dose-Response Relationship, Drug; Drug Therapy, Combination; Epinephrine; Female; Follicular Cyst; Oligopeptides; Progesterone; Propanolamines

The ovarian renin-angiotensin system may play an important role in follicular growth and maturation, as well as in the process of ovulation. The aim of this study was to investigate the effects of administration of a GnRH analogue to cows with ovarian follicular cysts on plasma renin concentrations and ovarian vascularization. This study was performed with 60 Friesian cows, which were diagnosed with follicular cysts, and randomly allocated into two groups: group A (treatment; n=30) received 2ml of lecirelin (Dalmarelin((R)) - Fatro), per head via sacro-coccygeal epidural, and group B (control; n=30) received 2ml saline solution (0.9% NaCl) per head by the same route. Blood samples were immediately collected prior to administration (T0) and then 24h (T1), 48h (T2) and 8 days (T3) after administration of the treatment, for both groups. Ovarian vascularization was evaluated utilizing Power Doppler on these same days in 10 animals from each group. The number of pixels detected by Power Doppler was used as an indicator of the degree of vascularization. Plasma renin concentrations remained relatively constant for the control (group B) animals, but increased as the sampling period progressed (NS) for the treated cows (group A). Similarly, there were no changes in ovarian vascularization (number of pixels) for the control cows, but vascularization increased throughout the sampling period in the treated animals. The number of pixels associated with cysts was significantly higher for treated compared to control cows at 24h after treatment (P<0.001). The epidural administration of a GnRH analogue was determined to be a highly effective therapy for follicular cysts (regression occurred in 82% of treated cows within 8+/-2 days after treatment, but in none of the control cows), which also enhanced ovarian vascularization.

Topics: Animals; Cattle; Cattle Diseases; Female; Follicular Cyst; Gonadotropin-Releasing Hormone; Injections, Epidural; Neovascularization, Physiologic; Oligopeptides; Ovary; Renin; Treatment Outcome; Ultrasonography

This study investigates the mechanisms of action by which a GnRH analogue may modulate the contractility of the bovine ovarian follicular wall. The in vitro evaluation of the spontaneous basal contractility of bovine preovulatory and cystic follicles was performed, followed by testing the effects of lecirelin, a GnRH analogue, on their basal contractility. Strips of tissue in isolated organ bath were employed. In addition, to better investigate the mechanism of action of lecirelin, the study of the effects of cumulative doses of nifedipine (a calcium channel blocker), phentolamine (an α-adrenoceptor antagonist) and reserpine (an inhibitor of the vesicular up-take of catecholamines) alone and, at the highest doses employed, associated to lecirelin, was set up. The results demonstrate that in basal conditions and after the addition of lecirelin, the strips from preovulatory follicles contract significantly more than strips from cysts. Furthermore, among the patterns of contractility evoked by the three drugs employed, the one induced by nifedipine was the only one unaffected by the addition of lecirelin. The data obtained provide the hypothesis that one of the main mechanisms of action of GnRH, could involve calcium channels.

Topics: Adrenergic alpha-Antagonists; Adrenergic Uptake Inhibitors; Animals; Calcium Channel Blockers; Cattle; Cattle Diseases; Female; Follicular Cyst; Gonadotropin-Releasing Hormone; In Vitro Techniques; Nifedipine; Oligopeptides; Ovarian Follicle; Phentolamine; Reserpine