The stability of the duration of the cycle of the seminiferous epithelium was determined by investigating incorporation of 5-bromodeoxyuridine into S-phase germ cells of normal and hemicastrated standard laboratory rats (Sprague-Dawley) and feral Brown/Norway rats (Rattus norvegicus). Feral rats were trapped on farms in the surroundings of Münster. The duration of the cycle of the seminiferous epithelium, determined at intervals of 12 days (3 h versus 12 days 3 h after 5-bromodeoxyuridine injection), was remarkably constant and similar in intact laboratory rats (12.49 +/- 0.05 days, n = 13, mean +/- SEM) and feral rats (12.44 +/- 0.06 days, n = 8). In hemicastrated laboratory and feral rats the duration of the cycle was similar to that in intact animals, indicating that hemicastration did not influence the kinetics of the seminiferous epithelium cycle. However, the coefficients of variation of the estimated duration of the cycle of the seminiferous epithelium were at least three times lower in hemicastrated rats (one testis from the same animal serving as reference point) compared with that of intact rats (the reference point based on the average staining frequency at 3 h). Overall, no significant differences between laboratory and feral rats could be observed with regard to testis weight and serum concentrations of FSH and testosterone. The number of cells per testis, determined by flow cytometry, was similar in laboratory and feral rats, except for a slight but significant difference in the haploid:tetraploid cell ratio (6.3 +/- 0.2 versus 7.5 +/- 0.3, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
We have investigated the antigonadotropic and antispermatogenic effects of exposure to a long-acting testosterone ester in the cynomolgus monkey model. Groups of five adult animals were exposed either to vehicle or to 10 mg/kg or 20 mg/kg testosterone buciclate (TB) over a 26-week period with injections given in weeks 0, 11 and 18. In week 26, testicular biopsy tissue was collected. Serum testosterone levels were in the upper normal range with 10 mg/kg TB and were approximately twofold higher with 20 mg/kg TB. The estradiol pattern followed that of testosterone and body weights increased in a testosterone-dependent manner. TB completely abolished serum LH bioactivity. Serum concentrations of FSH and inhibin-alpha were suppressed in a TB dose-dependent manner. During weeks 4-8 after the first injection, a rebound of FSH and inhibin but not bioactive LH secretion occurred. This rebound was followed immediately by a restimulation of testis size and sperm numbers. After the next TB injections these parameters were once again suppressed. Nadir testis size was 30-40% of baseline and animals were severely oligozoospermic or transiently azoospermic. Consistent azoospermia was not achieved. Quantitation of serum inhibin B, proliferating cell-nuclear antigen staining and flow cytometric analysis of germ cell populations revealed pronounced suppression of spermatogenesis in both TB-treated groups whereas androgen receptor expression remained unchanged. Testicular androgens levels, determined in week 26, did not differ among all three groups and did not correlate with sperm numbers, histological and immunocytochemical findings. All suppressive effects were fully reversed during the recovery period. We have concluded that pronounced suppression of primate spermatogenesis seemingly requires inhibition of FSH rather than testicular androgen levels, at least in this preclinical non-human primate model. For the purpose of male contraception, FSH inhibition appears mandatory.
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