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    Testicular effects of a postnatal GnRH antagonist in domestic cats

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    The aim of this study was to describe the histological effects of two high postnatal doses of the potent third-generation GnRH antagonist, acyline in the domestic cat testicle. Secondly, the physical, endocrine, and steroidogenic findings of this pharmaceutical protocol are also reported. Twelve postnatal littermate male kittens were administered acyline in a dose of 2.2 mg/100 g SC weekly for 2 weeks (ACY; n = 6), or placebo (PL; n = 6). All the animals were followed up until puberty when they were castrated. Serial faecal samples were collected until the age of 10 weeks for testosterone (T) measurement. The kittens achieved puberty without either age (236.5 ± 19.7 vs. 221.7 ± 23.7 days) or body weight (3.05 ± 0.15 vs. 2.78 ± 0.28 kg, P > 0.05) differences between ACY and PL, respectively. Acyline suppressed faecal T concentrations for 3 weeks (P 0.05). Histological assessment of the testes showed that ACY cats presented a reduced height of the epithelium (P < 0.01) due to the diminished number of germinal cells accompanied by an enlarged luminal area (P < 0.01) with cellular debris (P < 0.01). The immunostaining of P450c17 also appeared partially diminished in ACY testes.Fil: Grisolia Romero, Mariela Eugenia. Universidad Nacional de la Plata. Facultad de Cs.veterinarias. Centro de Fisiologia Reproductiva y Metodos Complementarios de Diagnostico.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Faya, Marcela Inés. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Marchetti, Cynthia Dayana. Universidad Nacional de la Plata. Facultad de Cs.veterinarias. Centro de Fisiologia Reproductiva y Metodos Complementarios de Diagnostico.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Korber, Hanna. Leibniz Universitat Hannover.; AlemaniaFil: Goericke Pesch, Sandra. Leibniz Universitat Hannover.; AlemaniaFil: Gobello, María Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de la Plata. Facultad de Cs.veterinarias. Centro de Fisiologia Reproductiva y Metodos Complementarios de Diagnostico.; Argentin

    Investigation of the role of CCR2 and activin A in fibrosis development during experimental autoimmune orchitis

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    EAO is a mouse model of chronic testicular inflammation and fibrosis, well reflecting pathologies seen in some forms of spermatogenic disturbances in men. This model is characterized by the destruction of testicular morphology, infiltration of the testicular interstitium by leukocytes, elevated levels of pro-inflammatory cytokines/ chemokines such as TNF, CCL2 (ligand for CCR2) and activin A, as well as loss of germ cells, all leading to fibrosis and subsequent infertility. TMs constitute the principal immune cell population in the testis and these cells play a critical role in maintaining tissue homeostasis. Increased numbers of TMs during testicular inflammation correlate with a higher incidence and severity of testicular damage. Because resident or macrophages newly recruited to the inflammatory lesions can produce a variety of pro-fibrotic factors including CCL2, TGF-β, TNF, PDGFs, MMPs or TIMPs, they are key players in fibrotic remodeling. CCL2 and CCR2 have a critical role in mediating the trafficking of monocytes, macrophages or bone marrow-derived fibroblasts to the site of injury. In the EAO model, an increase of CCL2 is observed not only in the testicular tissue but also in testicular interstitial fluid and conditioned medium from cultured TMs. Furthermore, activin A, a member of the TGF-β superfamily of cytokines, released mainly by SCs is increased in EAO testis and levels correlate with the severity of disease. Activin A stimulates resting macrophages to produce inflammatory mediators and promotes the expression of fibrosis specific genes in PTCs and NIH 3T3 fibroblasts in vitro. Based on these findings, we hypothesize that activin A in concert with CCR2 influences the development of testicular fibrosis by regulating the properties of macrophages, which in turn are an important source of pro-fibrotic factors in EAO. Therefore, the aims of this study are (1) to investigate the effect of CCR2 on the development of fibrosis during testicular inflammation, and (2) to analyze the influence of activin A on the fibrotic response in macrophages

    Long-term effects of GnRH agonists on fertility and behaviour

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    This review aimed to summarize the present knowledge about the effects of GnRH agonist slow-release implants (GnRH A-SRI) on fertility and behaviour in male and female dogs and cats with special focus on deslorelin.Following an initial stimulation of gonadotropin and testosterone secretion possibly associated with an improved semen quality, GnRH A-SRI induce long-term depression of fertility in male dogs and cats with, however, a large individual variation in onset and duration of efficacy especially in cats. The GnRH A-SRI furthermore interfere with testosterone-dependent/affected behaviour; a significant positive effect in reducing sexual behaviour and libido, hypersexuality, intermale dominance and excessive territorial urine marking has been described. Rates of improvement of the respective behaviour are comparable to those after surgical castration, making GnRH A-SRI a valuable option to predict castration-related effects on behaviour and to identify animals where surgical castration will not be beneficial. No effect has been seen in reducing aggression towards humans indicating the need for behavioural therapy to control this problem. Effects on spermatogenesis, steroidogenesis and behaviour have by now been shown to be fully reversible. Knowledge in females is more limited, and particularly, the initial induction of a possibly fertile oestrus and individual variation in duration of efficacy remain problems in bitches and queens treated for suppression of fertility. However, long-term suppression of oestrous cycle and fertility seems to be possible with induced effects shown to be reversible including restoration of normal fertility after the end of efficacy/GNRH A-SRI removal

    Antiprogestins in Small Animal Reproduction - More than Induction of Abortion in Dogs

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    Aglepristone is an antiprogestin that acts as a full progesterone receptor antagonist and therefore administration induces abolition of progesterone effects. Although the on-labelindication is termination of pregnancy in bitches up to 45 days after mating/LH peak only, there are various other off-label indications where its use has been successfully described. These include termination of pregnancy in queens and rabbits, induction of parturition in bitches, medical treatment of pyometra in bitches, queens, hamsters and guinea pigs and treatment of fibroadenomatosis. Additionally successful use has been described for gestagen-dependent insulin resistant diabetes mellitus, acromegaly in bitches, size reduction of benign canine vaginal tumours and reduction of proliferation of progesterone-receptor expressing mammary carcinomas. This review aims to give an update on possibilities and indicates limitations of the described use
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