| Alteration of gonadal functions after central GCV administration in Tg mice. Tg+GCV male mice display decreased testicular weight (A) and plasma testosterone concentrations after hCG (human chorionic gonadotropin) injection (B). Testicular histology of WT ctr (C), WT+GCV (D), Tg ctr (E) and Tg+GCV (F) male mice revealed alterations and vacuolization of seminiferous tubules after central GCV administration in Tg mice, scale bars, 50 µm Insets show a higher magnification image of a single seminiferous tube for each group of mice. Scale bar, 200 µm. Tg+GCV male mice display decreased serum LH concentration (G) while serum FSH concentration is not affected by the treatment (H). Data are expressed as the mean ± SEM, n≥3 for each group. *p<0.05, **p<0.01, ***p<0.001.

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... mice showed a stricking decrease in testes weight (Kruskal-Wallis, p<0.0001; Dunn's, p<0.05; Figure 4A). In addition, Tg+GCV mice showed a decline in the weight of preputial glands which produce pheromones . ...

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... a human chorionic gonadotropin (hCG) injection, a stimulation that elicits the release of the total testosterone content from the testes (36), a significant decrease of about 50% of the mean plasma testosterone levels was observed in Tg+GCV compared to control groups (Kruskal-Wallis, p=0.04, Dunn's, p<0.05; Figure 4B). Anatomical analysis of the testes sections showed that the three control groups, i.e. ...

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... analysis of the testes sections showed that the three control groups, i.e. WT ctr ( Figure 4C), WT+GCV ( Figure 4D) and Tg ctr ( Figure 4E), had normal seminiferous tubules. In contrast, the GCV treatment resulted in severe morphological alterations including vacuolization of seminiferous epithelium and no visible spermatozoa in the tube lumen in the Tg+GCV male mice ( Figure 4F). ...

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... analysis of the testes sections showed that the three control groups, i.e. WT ctr ( Figure 4C), WT+GCV ( Figure 4D) and Tg ctr ( Figure 4E), had normal seminiferous tubules. In contrast, the GCV treatment resulted in severe morphological alterations including vacuolization of seminiferous epithelium and no visible spermatozoa in the tube lumen in the Tg+GCV male mice ( Figure 4F). ...

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... analysis of the testes sections showed that the three control groups, i.e. WT ctr ( Figure 4C), WT+GCV ( Figure 4D) and Tg ctr ( Figure 4E), had normal seminiferous tubules. In contrast, the GCV treatment resulted in severe morphological alterations including vacuolization of seminiferous epithelium and no visible spermatozoa in the tube lumen in the Tg+GCV male mice ( Figure 4F). ...

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... ctr ( Figure 4C), WT+GCV ( Figure 4D) and Tg ctr ( Figure 4E), had normal seminiferous tubules. In contrast, the GCV treatment resulted in severe morphological alterations including vacuolization of seminiferous epithelium and no visible spermatozoa in the tube lumen in the Tg+GCV male mice ( Figure 4F). Interestingly, the seminiferous tubules of Tg+GCV mice only contained Sertoli cells, spermatogonia and some spermatocytes. ...

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... Figure 3). Moreover, no Gfap expression was detected in the testes of the control mice (data not shown) and the expression of the tk gene was undetectable in testes of Tg mice as shown by RT-PCR (Supplementary Figure 4), indicating that the anatomical defects observed in the testes were not due to a direct peripheral effect of GCV. These findings demonstrate that central GCV administration in Tg mice leads to a rapid and profound disruption of spermatogenesis and severe degradation of the testicular morphology. ...

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... there is a great variability because LH is secreted in a pulsatile and irregular manner, a significant decrease in the mean serum LH concentrations was observed in Tg+GCV male mice, (Kruskal-Wallis, p=0.04; Dunn's, p<0.05; Figure 4G) compared to control groups except for WT+GCV mice. In contrast, no significant differences were found in the mean levels of FSH, which regulate Sertoli cell function between the four groups (KruskalWallis, p>0.05; Figure 4H). ...

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... p<0.05; Figure 4G) compared to control groups except for WT+GCV mice. In contrast, no significant differences were found in the mean levels of FSH, which regulate Sertoli cell function between the four groups (KruskalWallis, p>0.05; Figure 4H). Together these data strongly suggest that 4 weeks of i.c.v. ...