Effects of zearalenone on in utero development in rats.

Zearalenone (ZE), an estrogenic mycotoxin produced by Fusarium graminearum or F. roseum, is one of the most common contaminants of cereal grains world-wide. The objective of this study was to determine the effects of ZE on in utero development of rats. Pregnant female Charles River Sprague-Dawley rats were gavaged once daily with ZE (in corn oil) at doses of 0, 1, 2, 4, or 8 mg/kg body weight on gestation days (GD) 6-19. All females survived to cesarean section on GD 20. At cesarean section, reproductive and developmental parameters were measured and blood was taken for hormone analysis. Dose-related decreases were seen in maternal feed consumption and body weight gain in all treated groups. Delayed fetal development was linked to maternal toxicity. Fetal body weight was significantly decreased in both sexes in all treated groups. ZE retarded skeletal ossification at 4 and 8 mg/kg. Fetal anogenital index (anogenital distance normalized for body weight) was increased in all treated groups, indicating an androgenic effect of ZE during fetal development. Fetal viability was significantly decreased at 8 mg/kg; significant decreases were observed in number of viable fetuses, and number of litters totally resorbed. At 4 and 8 mg/kg, maternal liver-body weight ratios were significantly increased and organ-brain weight ratios for weights of liver, heart, spleen, kidneys, and ovaries were significantly decreased. Gonadotropins (LH, FSH, and prolactin) and sex steroids (progesterone and estradiol) were analyzed from the blood serum obtained at cesarean section. LH in the 0, 1, 2, and 4 mg/kg groups showed minimal variation, and slightly increased at 8 mg/kg. FSH was decreased in the 1, 2, and 4 mg/kg groups, but the level at 8 mg/kg was slightly higher than the control level. Prolactin level was not affected at 1 mg/kg, slightly increased at 2 and 4 mg/kg, and significantly increased at 8 mg/kg. Progesterone was decreased at 2, 4, and 8 mg/kg and the decreases were significant at 2 and 4 mg/kg. Estradiol level was not affected at 1mg/kg, but dose-related decreases were observed at 2, 4, and 8 mg/kg. Only the 8 mg/kg level of estradiol was significantly decreased. In summary, ZE was maternally toxic and fetotoxic but not teratogenic. The increased anogenital distance observed in male and female fetuses was considered a hormonal change rather than a teratologic response. The increased anogenital distance indicated an androgenic effect. Based on the dose-related maternal and fetal toxicity in all treated groups, the NOEL for reproductive and teratogenic effects was less than 1 mg/kg.

Effects of deoxynivalenol (DON, vomitoxin) on in utero development in rats.

Deoxynivalenol (DON, vomitoxin), is one of the most common contaminants of cereal grains world-wide. The effects of DON on fetal development were assessed in Charles River Sprague-Dawley rats. Pregnant female rats were gavaged once daily with DON at doses of 0, 0.5, 1, 2.5, or 5 mg/kg body weight on gestation days (GD) 6-19. At cesarean section on GD 20, reproductive and developmental parameters were measured. All females survived to cesarean section. DON caused a dose-related increase in excessive salivation by the pregnant females, a reaction probably linked to the lack of emetic reflex in rats. At 5 mg/kg, feed consumption and mean body weight gain were significantly decreased throughout gestation, mean weight gain (carcass weight), and gravid uterine weight were significantly reduced, 52% of litters (12/23) were totally resorbed, the average number of early and late deaths per litter was significantly increased, average fetal body weight and crown-rump length were significantly decreased, the incidence of runts was significantly increased, and the ossification of fetal sternebrae, centra, dorsal arches, vertebrae, metatarsals, and metacarpals was significantly decreased. At 2.5 mg/kg, DON significantly decreased average fetal body weight, crown-rump length, and vertebral ossification. These effects may be secondary to maternal toxicity and the reduced size of the fetuses. The incidence of misaligned and fused sternebrae was significantly increased at 5.0 mg/kg. No adverse developmental effects were observed at 0.5 and 1.0 mg/kg. Dose-related increases in maternal liver weight-to-body weight ratios were observed in all treated groups (significant at 1, 2.5, and 5 mg/kg). The weight changes were correlated with dose-related cytoplasmic alterations of hepatocytes. The NOEL for maternal toxicity for this study is 0.5 mg/kg based on the dose-related increase in liver-body weight ratio at 1 mg/kg. The NOEL for fetal toxicity is 1 mg/kg based on the general reduction in fetal development at 2.5 and 5 mg/kg. DON is considered a teratogen at 5 mg/kg day in Sprague-Dawley rats based on the anomalous development of the sternebrae.

Effects of aminopentol on in utero development in rats.

UNLABELLED: Aminopentol (AP1), the backbone and main hydrolysis product of the mycotoxin fumonisin B1 (FB1), is present in corn-based foods which are consumed daily as a substantial part of the diet in some areas of the world. The toxicity of FB1 has been attributed to altered sphingolipid metabolism, but the toxicity of AP1 is less certain. Epidemiological correlations and in vitro studies have suggested that AP1 can increase neural tube defects (NTDs), but no in vivo developmental study of AP1 was done prior to this study. AP1 was given once daily to rats by gavage on gestation days (GD) 3-16 at doses of 0, 15, 30, 60, or 120 mg/kg. Reproductive and developmental parameters were measured at GD 17, one day after the last dose, and on GD 20. In addition, on GD 17, maternal and fetal tissues were analyzed for sphingolipid content. CONCLUSIONS: AP1 reduced dam body weight gain, but was less toxic than FB1. AP1 was not teratogenic, did not affect tissue sphingolipid ratios, did not alter reproduction or development of fetuses, and produced no dose-related histopathological effects in dams.

Characterization of the effect of deoxynivalenol on selected male reproductive endpoints.

The effect of deoxynivalenol (DON) exposure on male reproductive function was assessed in the rat. Male rats were divided into a control group (n=15 rats) and four treatment groups (0.5 mg/kg, n=15; 1.0 mg/kg, n=15; 2.5 mg/kg, n=15; and 5.0 mg/kg DON, n=16) and exposed to DON daily for 28 days via gastric intubation. Both body weight gain and the final body weight of animals in the 5.0 mg/kg dose group and feed consumption in animals in the 2.5 mg/kg and 5.0 mg/kg dose groups were significantly reduced compared to controls. Fluid consumption was not affected in any of the treated groups. Epididymal and seminal vesicle weights expressed per gram of body weight and brain weight were significantly reduced, compared to control weights, in animals from the 2.5 and 5.0 mg/kg dose groups while prostate weight expressed per gram of brain weight and body weight was significantly lower than controls only in the 5.0 mg/kg dose group. A statistically significant, dose-related decrease in homogenization resistant testicular spermatid counts, spermatid numbers, absolute cauda epididymal sperm numbers and cauda epididymal sperm numbers per gram of cauda epididymis was observed in the 5.0 mg/kg DON treatment group. Sperm tail abnormalities (broken tails) in the 5.0 mg/kg dose group were significantly higher than in the control group. Sperm swimming speed (VSL and VCL) was significantly increased only in the 2.5 mg/kg dose group. Serum FSH and LH concentrations were increased in a dose dependent manner across all treated groups while serum testosterone concentrations were decreased in a dose-related manner across all dose groups. An increase in germ cell degeneration, sperm retention and abnormal nuclear morphology was observed in the 2.5 mg/kg and 5.0 mg/kg dose groups. Treatment related effects included lesions in the non-glandular stomach, thymic lymphoid depletion and splenic hematopoiesis in the 5.0 mg/kg treatment group.