Gestational Exposure to Ethane Dimethanesulfonate: RESULTS(1)

Administration of 160 mg/kg EDS during GD 11-17 did not affect overall maternal weight gain; however, it did decrease neonatal body weight on PND 1 by 15%, 1.72 vs. 1.47 g. This decrease was statistically significant and persisted in both the prepubertal and adult offspring. Both AGD and the onset of preputial separation, sensitive indicators of circulating androgens or variations in androgen responsiveness during sexual differentiation, were evaluated in male offspring. On PND 1 and PnD 82, 9-12 litters were represented per treatment group per time point. On both PND 1 and PnD 82, AGD was decreased in EDS-exposed males, 2.3 vs. 2.2 and 17.2 vs. 14.7 on PND 1 and PND 82, respectively. However, these differences were not significant after adjusting for the EDS-induced decreases in body weight by covariate analysis. Likewise, the observed delay in the onset of puberty (PND 26 vs. PND 30) was not delayed in males exposed prenatally to EDS when co-variate analysis was run to correct for the decrease in body weight.

Initial studies were performed to evaluate endogenous whole-body T levels in the fetal CD-1 mice utilized in this study. In control mice T began to increase beginning on GD 15, peak on GD 16 at 1.0 ± 0.1 pg/mg of fetus, and subsequently decrease until PND 4 (data not shown). In male offspring prenatally exposed to EDS, the T levels on GD 15 and 16 were decreased, compared with controls (Fig.1). Litter means for T levels on Gd 15 were 0.94 ± 0.01 vs. 0.84 ± 0.02 pg/mg of fetus and on GD 16 were 1.45 ± 0.17 vs. 0.99 ± 0.02 pg/mg of fetus for control and EDS, respectively. By GD 17, T levels were comparable with control.

Although seminal vesicle weight was not affected, the weights of other T-dependent organs, i.e., testis and epididymis, of adult mice were decreased in a body weight-independent manner (Fig. 2). Enumeration of cauda epidid-ymal sperm from adult mice revealed a decrease in sperm; 17.9 X 106 ± 9.0 X 105 vs. 2.7 X 106 ± 6.7 X 105 cauda epididymal sperm for males exposed to control and EDS, respectively.
Fig1Gestational Exposure to Ethane-1
FIG. 1. Effect of gestational EDS exposure on whole-body T levels in the fetal male mouse. The endogenous GD 16 T peak is significantly diminished with treatment. Values represent litter means ± SEM; statistical significance (P < 0.05 = *) is indicated; N = 3-4 per time point.

Fig2Gestational Exposure to Ethane-2
FIG. 2. Effect of EDS exposure on reproductive organ weights and cauda epididymal sperm number. A) Effect of EDS on reproductive organ weights of adult (PND 82) male mice. Values represent litter means ± SEM; statistical significance (P < 0.001 = *) is indicated; N = 12 and 11 for vehicle and EDS-exposed groups, respectively. B) Effect of EDS on cauda epididymal sperm numbers in adult (PND 82) male mice. Values represent litter means ± SEM; statistical significance (P < 0.0001 = *) is indicated; N = 9.

Category: Dimethanesulfonate

Tags: Leydig cells, testis, testosterone, toxicology