Article

Effects of the GnRH antagonist acyline on the testis of the domestic cat (Felis catus)

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Abstract

The aim of this study was to describe the effects of a single dose of the gonadotrophin releasing hormone (GnRH) antagonist acyline on testicular characteristics of the domestic cat. Twelve mature cats were orchidectomised unilaterally (right testis) on Day -7 (n=7) or Day 15 (n=5). On Day 0, 330 μg/kg acyline was administered s.c. to all the animals. Left orchidectomy was carried out on Day 15 (n=2), Day 30 (n=4) and Day 60 (n=6). Sperm were recovered from the epididymis and the testes were evaluated grossly, histologically and immunohistochemically. Significant differences (P<0.05) were found between days for epididymal sperm motility, vigor, abnormal morphology, germinal epithelium height, spermatocytes, spermatids, spermatozoa, lumen and cellular debris. Conversely, no significant differences were found for gross testicular and tubular characteristics, spermatogonia, Sertoli and Leydig cells and intertubular compartments. It was concluded that a single dose of acyline reversibly impaired spermiogenesis, spermatocytogenesis and sperm motility for 2 weeks.

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... 36,46 Kedilerde GnRH antagonistleri östrus davranışlarını baskılamak veya östrusları ertelemek amacıyla kullanılabileceği yapılan birçok çalışmayla ortaya konulmuştur. [47][48][49][50] Kedilerde yapılan çalışmalarda genellikle antide ve acyline gibi GnRH antagonistlerinin kullanıldığı bildirilmektedir 47,49,50 Pelican ve ark. çalışma gruplarından 8 dişi kediye GnRH antagonisti olan antide'yi 6 mg/kg dozda 15 gün arayla olacak şekilde iki kez uygulamışlar ve günlük dışkı örneklerinde östradiol seviyelerini ölçmüşlerdir. ...
... 36,46 Kedilerde GnRH antagonistleri östrus davranışlarını baskılamak veya östrusları ertelemek amacıyla kullanılabileceği yapılan birçok çalışmayla ortaya konulmuştur. [47][48][49][50] Kedilerde yapılan çalışmalarda genellikle antide ve acyline gibi GnRH antagonistlerinin kullanıldığı bildirilmektedir 47,49,50 Pelican ve ark. çalışma gruplarından 8 dişi kediye GnRH antagonisti olan antide'yi 6 mg/kg dozda 15 gün arayla olacak şekilde iki kez uygulamışlar ve günlük dışkı örneklerinde östradiol seviyelerini ölçmüşlerdir. ...
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... Whereas four studies are available about the use of GnRH antagonists in queens (Pelican et al. 2005(Pelican et al. , 2008(Pelican et al. , 2010Risso et al. 2010), only one study describes the use in tom cats (Garcia Romero et al. 2012) so that it can be stated that at the moment, GnRH antagonists are predominantly of scientific interest andalthough results are promisingare lacking broad clinical experience. In the tom, a single subcutaneous (SC) injection of acycline (330 lg/kg) caused a significant reversible impairment of spermiogenesis, spermatocytogenesis and motility for 2 weeks, but had no influence on gross testicular and tubular characteristics including Sertoli and Leydig cells (Garcia Romero et al. 2012). ...
... Whereas four studies are available about the use of GnRH antagonists in queens (Pelican et al. 2005(Pelican et al. , 2008(Pelican et al. , 2010Risso et al. 2010), only one study describes the use in tom cats (Garcia Romero et al. 2012) so that it can be stated that at the moment, GnRH antagonists are predominantly of scientific interest andalthough results are promisingare lacking broad clinical experience. In the tom, a single subcutaneous (SC) injection of acycline (330 lg/kg) caused a significant reversible impairment of spermiogenesis, spermatocytogenesis and motility for 2 weeks, but had no influence on gross testicular and tubular characteristics including Sertoli and Leydig cells (Garcia Romero et al. 2012). ...
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... However, more studies are necessary to determine the duration of immunity and true rate of efficacy of GnRH immunocontraception in cats. More recently, the use of a single dose of GnRH antagonist (330 mg/kg acycline) was efficient to impair spermiogenesis, spermatocytogenesis, and sperm motility for 14 days [6]. In addition, the use of a GnRH agonist implant (4.7 mg deslorelin; Suprelorin, Virbac, France) during 252 days proved to be effective to reduce testis size, libido, mating behavior, and urine marking. ...
... It was also proved that in dogs, a single administration of this drug prevented the pituitary-gonadal axis responding to GnRH agonistic (buserelin) stimulation for 14 days (Garcia Romero et al. 2012a). It should be also noted that in cats, a single dose of acyline reversibly impaired spermiogenesis, spermatocytogenesis and sperm motility for 2 weeks (Garcia Romero et al. 2012b). Up to now, GnRH antagonists have not been widely introduced into veterinary practice mainly due to high costs of the drug and the necessity of relatively frequent administration. ...
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Quantification of changes in semen may give insight into the testosterone (T)-induced disruption of spermatogenesis in man. A model analogous to flushing of sperm from the genital tract after vasectomy was used to quantify the time course of semen changes in subjects participating in male contraceptive trials using 800 mg T-implant (n = 25) or 200 mg weekly intramuscular injection (IM-T; n = 33). A modified exponential decay model allowed for delayed onset and incomplete disruption to spermatogenesis. Semen variables measured weekly during a 91-day period after initial treatment were fitted to the model. Sperm concentration, total count, motility and morphometry exhibited similar average decay rates (5 day half-life). The mean delay to onset of decline in concentration was 15 (IM-T) and 18 (T-implant) days. The significantly longer (P < 0.005) delays deduced for the commencement of fall in normal morphology (41 days), normal morphometry (40 days) and sperm viability (43 and 55 days), and the change of morphometry to smaller more compact sperm heads are consistent with sperm being progressively cleared from the genital tract rather than continued shedding of immature or abnormal sperm by the seminiferous epithelium. A significant negative relationship was found between lag time and baseline sperm concentration, consistent with longer sperm-epididymal transit times associated with lower daily production rates.
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The primary objective was to assess the effects and clinical safety of a single high-dose of the third generation GnRH antagonist, acyline, on testicular characteristics in male dogs. Seven dogs were followed up weekly for six, 2-week periods (-2, -1, 1, 2, 3 and 4). At the end of the second period, they were given acyline (330 microg/kg sc). Responses to treatment varied among individual animals. Testicular consistency and scrotal diameter were slightly diminished (P>0.05) in Periods 1, 2, and 3. Libido and erection decreased during Periods 1 and 2 (P<0.05). Second and third fractions of the ejaculate volume, sperm count and motility varied throughout periods (P<0.01); there was a clear impairment of these parameters (< or =0.2 mL, < or =0.6 mL, < or =0.5 million/mL and < or =30%, respectively) around the second week of Period 1, followed by slow improvement (to the end of the study). Semen volumes and motility diminished during Period 1 (P<0.05). Sperm count decreased during Periods 1, 2, and 3, relative to Periods -2 and -1 (22.7+/-11.7, 62.8+/-19.9, and 51.0+/-25.4 versus 235.7+/-63.3 and 315.5+/-27.3, respectively; P<0.05; (L.S.M.+/-S.E.M.). Morphologically abnormal sperm increased during Periods 2 and 3 (up to 64.9+/-2.6%; P<0.05). Throughout the study, no dog had hematological, biochemical, local, or systemic side effects. In conclusion, a single high-dose acyline treatment severely decreased semen quality with no adverse effects.