-Changes in blood parameters, especially those related to blood coagulations, were examined on gestational days (GDs) 6, 18 and 28 in Japanese White rabbits. As compared with the non-pregnant group, the following changes were observed in the pregnant group. For blood coagulation-related parameters, fibrinogen, platelets and antithrombin time III (ATIII) was significantly increased on GD 18 and/or GD 28, and activated partial thromboplastin time (APTT) was significantly prolonged on GDs 18 and 28. For the other hematological and blood chemical parameters, hemoglobin and hematocrit values were significantly decreased on GDs 18 and 28. Reticulocyte counts significantly and prominently increased on GD 18 and then decreased to significantly lower levels than those in the non-pregnant group on GD 28. Eosinophils and basophil showed significant decreases on GD 18 and/or GD 28. The serum progesterone concentration reached its highest level on GD 18. Total protein (TP), albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), cholesterol, calcium, glucose and blood urea nitrogen were significantly decreased on GD 18 and/or GD 28. These results were almost similar to those in the pregnant New Zealand White rabbits (Mizoguchi et al., 2010).
-In our previous study on the effects of restricted feeding on pregnant rabbits (Matsuoka et al., 2009), animals given 20 g/day of diet on and after gestation day 6 (GD 6) showed significant changes in blood coagulation-related parameters suggesting a tendency to bleed and a decrease in serum concentration of progesterone, an important factor to maintain pregnancy, on GD 22, and a half of them showed serum progesterone concentrations less than 4.0 ng/ml which resulted in abortions on and after GD 23. In the present study, the effects of restricted feeding of 20 g/day from GD 6 to GD 22 on embryo-fetal and placental development on GD 23 as well as on blood coagulation-related parameters and serum progesterone concentrations on GD 22 were examined in pregnant rabbits. As compared with the non-restricted feeding (Not-treated, NT) group, the restricted feeding (RF) group showed lower values of platelets, fibrinogen, activated partial thromboplastin time (APTT) and antithrombin III (ATIII) and a longer prothrombin time (PT), reflecting an inhibition of blood coagulation, and a decrease in serum progesterone concentration on GD 22. Cesarean section performed on GD 23 revealed that the RF group showed a tendency towards an increase in the embryo-fetal death index and lower body weights and placental volumes compared with the NT group. Histological examination of the placenta in the RF group revealed that the labyrinth zone was thin and many glycogen-containing cells still remained in the basal zone, suggesting a delay in placental growth.
Ethyl tertiary-butyl ether (ETBE) is commonly used as an oxygenated gasoline additive. In this study, the prenatal developmental toxicity of ETBE was determined in rabbits. New Zealand white rabbits were given ETBE by gavage at 100, 300, or 1,000 mg/kg/day on gestational days (GDs) 6-27, and the pregnancy outcome was determined on GD 28. Neither death nor abortion occurred in the pregnant rabbits at any dose. Slightly and significantly suppressed maternal body-weight gain and transiently decreased maternal food consumption were found at 1,000 mg/kg/day during the administration period. At this dose, no changes in clinical or macroscopic finding were noted in dams. No treatment-related changes were observed in any dam treated at 300 mg/kg/day or less. There was no significant effect of ETBE on the numbers of corpora lutea, implantations, live fetuses, resorptions and dead fetuses, incidences of pre- and postimplantation loss, viability of fetuses, fetal body weight, sex ratio of fetuses, or weights of gravid uteri. No significant difference was detected in the incidences of fetuses with malformations or variations between the ETBE-treated and control groups. Also, no adverse effects on the progress of ossification were noted in fetuses of dams given ETBE. Based on these findings, it is concluded that the no observed adverse effect levels of ETBE were 300 mg/kg/day for dams and 1,000 mg/kg/day for fetuses in rabbits.
We surveyed 1053 pregnant rabbits of the Kbl:NZW strain collected from 27 developmental toxicity studies to reveal the prevalence and significance of gastric hairballs. The incidence of hairballs was 2/525 (0.4%) in the control group and 17/528 (3.2%) in the high dose group. In the high dose group, 16 dams resulted in abortion or death. In addition, decreases in body weight and food consumption were more severe in dams with hairballs than in their group-mates without hairballs.
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