Fachbereich Veterinärmedizin



    Zur Untersuchung der Fertilität der männlichen Ratte unter dm Einfluß des Virustatikums Ganciclovir (1996)

    Klug, Annette
    Berlin, 1996 — 112 Seiten
    Institut für Tierschutz und Tierverhalten

    Königsweg 67
    Gebäude 21, 1. OG
    14163 Berlin
    Tel.: +49 30 838 62901 (Sekretariat)
    email: tierschutz@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    The physiological function of the male reproductive system depends on a multitude of factorsand is a very sensitive biological process. The reproductive capacity of the human is considerablylower than those of conventional animal models. Therefore the use of natural mating of laboratoryanimals is an insensitive test for the risk assessment for human male fertility. The aim of thisinvestigation was the choice of sensitive tests for male fertility. The duration of treatment and theplaning of an efficient time schedule for investigations were also of importance.We chose ganciclovir as a model substance to cause damage of the male reproductiveorgans. Male rats were treated either with 60 mg Ganciclovir / kg bodyweight on five days(GAN 60/5) or with 100 mg Ganciclovir / kg bodyweight three times on one day(GAN 100/3). We investigated bodyweight, weight of selected organs. results of naturalmating, number of spermatids and spermatozoa, sperm morphology, morphology of thetestes and the concentration of ganciclovir in the testes. All investigations were done 2, 4, 6,8, 16 and 24 weeks after the first treatmentThe results are given below:I . No signs of a general toxic effect occured in both treatment groups.2 The mating index in both treatment groups did not differ at any time statistical significantly fromthe control.3. Treatment with ganciclovir caused a slight but statistical significant prolongation of the fertilityindex in the group GAN 100/3, which might be considered as a sign of subfertility.4 In the group GAN 60/5 the pregnancy index was only lowered after eight weeks, in the GAN100/3 group it was reduced between the 6th and 16th week after treatment.;. In the group GAN 60/5 the number of spermatids was statistical significantly reduced betweenthe 4th and 16th week in the group GAN 100/3 it was lowered from the 4th week until the end of theinvestigation.6. The percentage of morphological abnormal spermatozoa increased statistical significantly fourweeks after treatment. The percentage of spermatozoa with aberrations of the heads remainedelevated until the end of the investigation.7. Twenty-four hours after the treatment with ganciciovir damage of different gemtinal cells wasobserved histologically. There was no complete reversion of the destruction of stemspermatogonia, which was proven during the investigation by timepoint and severity of changes.8. Two hours after the treatment ganciclovir was detectable in the testes. Its highest concetrationwas measured after four hours; the elimination of the substance from the testes followed theelimination from plasma.Taking these results the following points can be made:1. A short-terrn treatment with a concentration of substance not causing a general toxic effect caninduce severe destruction of the male reproductive organs. Choosing the time for investigationafter the treatment at least three times the duration of one cycle of the seminiferous epithelium isuseful to get some ideas of the potential sites and mechanisms of action of the agent and allowsconclusions concerning the reversibility of the changes.2. Natural mating of laboratory animals has been proven to be the most insensitive test fordetecting adverse effects of a substance on male reproductive organs.3. There was no impairment of the reproductive capacity of treated male rats down to a percentageof about 10 % intact spermatozoa in the cauda epididymis compared to the controls4. Useful tests for the detection of effects on the male reproductive organs in the scope oflarge-scale toxicity studies are the determination of testes weights and of the number of spermatidsresistent to homogenisation, and the morphological investigation of spermatozoa. Evaluations oftesticular histology may show even slight aberrations soon after treatment, but they are not easy toperform and the degree of the damage is hardly to quantify. The determination of the number ofspermatozoa in the cauda epididymis may be neglected regarding the high physiologicalfluctuation of this test.