| Abstrakt: |
A 90-day/one-generation reproduction study was conducted in male and female Crl:CD BR rats using dietary levels of 0, 0.05, 2.5, 10, and 50 ppm 17β-estradiol. The goals of this study were to set dose levels and evaluate several mechanistic end- points for inclusion in multigeneration reproduction and com- bined chronic toxicity/oncogenicity studies with 17β-estradiol. In this report we discuss the effects of dietary 17β-estradiol exposure on serum hormonal levels and sperm parameters from P1 and F1 male rats. Sperm parameters were also evaluated in recovery P1 and F1 male rats that were fed control diets for 105 and 103 days, respectively, following 97 and 86–94 days of estradiol exposure, respectively. Measurement of Sertoli cell number from F1 male rats was performed to test the hypothesis that in utero exposure to estrogens will decrease Sertoli cell number and sperm production. Other findings from this 90-day/ one-generation reproduction study are summarized elsewhere. 17β-Estradiol produced a dose-dependent decrease in body weight in P1 male rats at ≥2.5 ppm and in the F1 male rats at 2.5 ppm. This decrease in body weight was due to a combination of reduced food consumption and food efficiency. In the recov- ery P1 males, body weight increased in the affected groups, albiet not to control levels, due to food consumption returning to control levels accompanied by an increase in food efficiency. However, in F1 males there was no corresponding rebound in body weight. In the P1 rats, exposure to 17β-estradiol decreased testis and epididymis weights in the 10 and 50 ppm groups, while no effects were seen in the P1 2.5 ppm group. In contrast, epididymis weights in the F1 and F1 recovery 2.5 ppm groups were statistically decreased; however, there were no histopatho- logical effects observed. The decreases in testis weights in the P, generation correlated with histopathologic evidence of intersti- tial cell atrophy and seminiferous tubule degeneration and reduced sperm production. Correlative changes in the epidid-ymides of P1 rats were characterized by oligospermia or asper-mia, the presence of germ cell debris in the lumen of tubules, and atrophy of epididymal tubules. 17β-Estradiol decreased testicular spermatid numbers, epididymal sperm numbers, and sperm motility in the P1 males in the 10 and 50 ppm groups, but not in the 2.5 ppm group. Following a 105-day recovery period in the P1 males, all sperm parameters and reproductive organ weights returned to control values except for the epididymal sperm count. Overall, the decline in testicular spermatid and epididymal sperm numbers in the P1 rats correlated with the reduced organ weights and the observed histopathological changes and appeared primarily related to the decrease in serum testosterone levels. In the F1 rats, no significant decreases were noted in the testicular spermatid number but a slight decrease in epididymal sperm number was seen in the 2.5 ppm group, which showed no evidence of recovery. Using morphometric analysis, no change was seen in the number of Sertoli cell nuclei per testis in F1 males. The pattern of hormonal responses seen in this study was characteristic of an estrogen receptor agonist such as 17β-estradiol: increased serum prolactin and decreased testosterone, luteinizing hormone, and follicle stimulating hormone levels. The data demonstrate that in utero and postnatal dietary administration of 17β-estradiol at levels which increased serum estradiol levels to approximately 400% of control and decreased testosterone levels to 33% of control did not reduce the number of Sertoli cell nuclei per testis. [ABSTRACT FROM PUBLISHER] |
