Assessment of quantitative dual-parameter flow cytometric analysis for the evaluation of testicular toxicity using cyclophosphamide- and ethinylestradiol-treated rats.

Abstract

-In the drug discovery process, effects to the human spermatogenesis must be fully evaluated before the first human trial. To estimate testicular toxicity, histopathological evaluation has been recommended in addition to the traditional mating procedure. However, it is laborious and time-consuming. Flow cytometric analysis (FCM) has also been applied to estimate testicular toxicity because of its speed, simplicity, and the objectivity of the data. Using cyclophosphamide (CP)-and ethinylestradiol (EE)-treated rat testis, we attempted to validate our dual-parameter, DNA ploidy and cell-size FCM, in a high-throughput toxicity study. Our results showed that CP damaged some spermatogonia and some early meiotic spermatocytes and EE caused severe decrease of spermatogenic cells except for spermatogonia as well as marked decrease of somatic cells, most probably Leydig cells. This is the first report discriminating between the changes of spermatogonia and that of somatic cells with FCM analysis. These results demonstrate that this method is a very useful and powerful tool to assess testicular toxicity, especially in high-throughput toxicological studies.

Interventional effects of squid ink polysaccharides on cyclophosphamide-associated testicular damage in mice

“…Previous studies reported that long-term low-dose CP exposure should result in reductions in body weight, testis weight, and testis index in humans or animals (17), and reduction of sperm count and quality (18), which would affect growth of offspring and increase the percentage of deformities therein. Testis weight is connected with quantities of different differentiational spermatids (19). We found results here that were consistent with those in our previous work which indicated that CP exposure resulted in decreases in sperm count and survival ratio, an increased sperm abnormality ratio, as well as signifi cant reductions in body weight, testis weight and index in CP-treated mice, which also agreed with current data (3,4,9,20).…”

Black Grape Seed Extract Modulates Fluoxetine-Induced Oxidative Stress and Cytotoxicity in the Mouse Testis

“…Thus, the marked reduction in body weight that occurs with FLX can be explained by decreased intestinal absorption, leading to the diminishment of necessary nutrients. On the other hand, it is known that testicular weight largely depends on the population of differentiated spermatogenic cells (27). Therefore, FLX-induced significant testicular weight loss can be attributed to testicular hypocellularity and spermatogenesis suppression, as well as to the reduced availability of androgens, as confirmed by our findings.…”

Reduction of spermatogenesis in mice after tributyltin administration

“…duction (Katoh et al, 2002). In the present study, histopathological findings in the testis showed significant degenerative alterations in 50 g/kg groups.…”