Effect of estrogen on rat placental development depending on gestation stage.

We examined the sequential histopathological changes in the placenta from rats exposed to estrogen. 17 β-estrogiol-3-benzoate was intraperitoneally administered at 100 μg/animal/day during GD 6 to GD 8 (GD6-8 treated group), GD 9 to GD 11 (GD9-11 treated group) and GD 12 to GD 14 (GD12-14 treated group), and the placentas were sampled on GDs 11, 13, 15, 17, and 21. Fetal mortality rates were increased up to approximately 50% in the GD6-8 and 9-11 treated groups, but there was no change of fetal weight on GD 21.

Carcinogen-induced Thyroid Proliferative Lesions in Wistar Hannover GALAS Rats with Thyroid Dysplasia.

Incidences and morphological features of thyroid proliferative lesions induced by carcinogens in Wistar Hannover GALAS rats (GALAS rats) showing normal growth with or without thyroid dysplasia were examined. All thyroid tissue samples were obtained from our recently conducted study using male GALAS rats treated with 5 carcinogens according to the medium-term multiorgan carcinogenicity bioassay protocol (called DMBDD treatment). In the DMBDD-treated rats, thyroid dysplasia was found in 9 out of 114 rats.

Toxicological pathology in the rat placenta.

The placenta grows rapidly for a short period with high blood flow during pregnancy and has multifaceted functions, such as its barrier function, nutritional transport, drug metabolizing activity and endocrine action. Consequently, the placenta is a highly susceptible target organ for drug- or chemical-induced adverse effects, and many placenta-toxic agents have been reported. However, histopathological examination of the placenta is not generally performed, and the placental toxicity index is only the placental weight change in rat reproductive toxicity studies.

Effect of cisplatin on rat placenta development.

We examined the sequential histopathological changes in the placenta from rats exposed to cisplatin. Cisplatin was intraperitoneally administered at 2 mg/kg/day during GDs 11-12 (GD11,12-treated group), or GDs 13-14 (GD13,14-treated group), and the placentas were sampled on GDs 13, 15, 17 and 21. Fetal mortality rates were increased up to approximately 65% from GD 17 onward, and fetal weights were decreased on GD 21 in the GD11,12-treated group.

The use of an automated hematology analyzer to observe cell growth in the chromosome aberration test using human lymphocytes.

Human lymphocytes have been frequently used for in vitro chromosome aberration or micronucleus tests on whole-blood culture. However, it is difficult to observe or confirm the cell growth of lymphocytes just before chemical treatment compared with cultured cell lines, such as CHL or CHO cells. In order to overcome this drawback of using whole-blood culture, we investigated a possibility of using an automated hematology analyzer (AHA) (Sysmex XT-2000i, SYSMEX Corp.

The impairment of metrial gland development in tamoxifen exposed rats.

We examined the sequential histopathological changes in the placenta from rats exposed to tamoxifen. Tamoxifen was administered intraperitoneally at doses of 0 and 2 mg/kg/day on gestation days (GDs) 8, 9 and 10, and the placentas were sampled on GDs 11, 13, 15, 17, and 21. The fetal mortality rates in the tamoxifen group were increased up to 56%.

The relationship between fetal growth restriction and small placenta in 6-mercaptopurine exposed rat.

In order to investigate the effect of placental size on fetal intrauterine growth retardation (IURG), we examined the morphology and alterations in the expression of glucose transporter in the placentas of rats exposed to 6-mercaptopurine (6-MP). 6-MP was administered orally at 0 and 60 mg/kg/day on gestation day (GD) 9, 11, 13 or 15, and the placentas were sampled on GDs 17 and 21. The main findings in the treated groups were small placenta caused by mitotic inhibition and apoptosis, fetal resorption and IUGR with or without some malformations.

Multi-endpoint genotoxic assay using L5178Y (Tk(+/-) -3.7.2c) cells.

When the mouse lymphoma Tk assay (MLA) provides a positive result, its cause can be roughly estimated by examining colony sizes. An increase in the number of large colonies means that the compound tested has point mutational potential, while an increase in small colonies indicates the potential for chromosome aberration. However, it was found to be difficult to clearly judge this in the case of caffeine known as a clastogen lacking the potential of point mutation.

Histopathological effect of ketoconazole on rat placenta.

In order to investigate the morphological effects of ketoconazole on hypertrophied placentas, we examined the sequential histopathological changes in the placenta from rats exposed to ketoconazole. Ketoconazole was administered orally at 0 and 25 mg/kg/day during gestation days (GDs) 12 to 14, and the placentas were sampled on GDs 15, 17 and 21. All dams showed neither effect on body weight nor any abnormal clinical signs during the experimental period.

Effect of 6-mercaptopurine on rat placenta.

In order to investigate the toxic effects of 6-mercaptopurine (6-MP) on placental development, we examined sequential morphology in the placentas from rats exposed to 6-MP. 6-MP was intraperitoneally administered at 60 mg/kg during gestation days (GDs) 11 to 12, and the placentas were sampled on GD 13, 15 or 21. In the 6-MP-treated group, maternal body weight suppression, increased death embryo/fetus ratio and some malformations were observed.

Carcinogenic risk of copper gluconate evaluated by a rat medium-term liver carcinogenicity bioassay protocol.

Carcinogenic risk and molecular mechanisms underlying the liver tumor-promoting activity of copper gluconate, an additive of functional foods, were investigated using a rat medium-term liver carcinogenicity bioassay protocol (Ito test) and a 2-week short-term administration experiment. In the medium-term liver bioassay, Fischer 344 male rats were given a single i.p.

Possible carcinogenic risks of copper gluconate and their prevention by co-administered green tea catechins evaluated by a rat medium-term multi-organ carcinogenicity bioassay protocol.

Carcinogenic risks of copper gluconate, green tea catechins and their combined exposure were evaluated using a rat medium-term multi-organ carcinogenicity bioassay protocol. Male BrlHan:WIST@Jcl (GALAS) rats were given N-nitrosodiethylamine (DEN), N-methylnitrosourea (MNU), 1,2-dimethylhydrazine (DMH), N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) and 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN) for a total multiple initiation period of 4 weeks (DMBDD treatment). Rats were then given a diet containing copper gluconate at a concentration of 0, 10, 300, 3000 or 6000 ppm with or without a co-administration of catechins starting 1 week later by admixing in the drinking water at a concentration of 5000 ppm.

Busulfan-induced apoptosis in rat placenta.

In order to investigate the effects of busulfan on the placenta, we examined the sequential histopathological changes in the placenta from rats exposed to busulfan during gestation days (Days) 12-14. Busulfan was intraperitoneally administered at 10 mg/kg on Days 12, 13 and 14, and the placentas were sampled on Day 13.5, 14.

Indole-3-acetic acid induces microencephaly in mouse fetuses.

To determine the effect of indole-3-acetic acid (IAA), known as natural auxin, on developing fetus, pregnant mice were injected with 500 or 1000 mg/kg on various gestation days (Days). With the repeated treatment during Days 7-15, the fetal brains exhibited a reduction in size and weight in a dose-dependent manner on Day 18. Histopathologically, hypoplasia of the cortical plate, piriform cortex, hippocampus and thalamus were observed.

Effect of indole-3-acetic acid derivatives on neuroepithelium in rat embryos.

Indole-3-acetic acid (IAA), a natural auxin, induces microencephaly in rats exposed to IAA during gestation days (Days) 12-14, corresponding to the early stage of cerebral cortex development. The purpose of this study was to examine the effects of 5 IAA derivatives administration in pregnant rats on neuroepithelial cells in the embryos. N-Methylindole-3-acetic acid (1Me-IAA), 2-Methylindole-3-acetic acid (2Me-IAA), 2-Methyl-5-methoxyindole-3-acetic acid (2Me-5MeO-IAA), 5-Methoxyindole-3-acetic acid (5MeO-IAA), Indole butyric acid (IBA), and IAA were administered at 1,000 mg/kg except for 2Me-IAA at 500 mg/kg on Days 12, 13 and 14, and then embryos/fetuses were harvested on Day 14.

Indole-3-acetic acid induces microencephaly in rat fetuses.

Indole-3-acetic acid (IAA), known as natural auxin, induces cleft palate in rodents. However, there has been no report about the neurodevelopmental toxicity of IAA in rats. In the present study, we found microencephaly in the fetuses from the rats exposed to IAA.

Histopathological findings of cleft palate in rat embryos induced by triamcinolone acetonide.

Triamcinolone acetonide (TAC), a synthetic glucocorticoid, induces cleft palate resulting from poor development of palatal shelves in mice. However, TAC has no effect on medial edge epithelial cells (MEE cells) in secondary palatal shelves. In the present study, we examined the relationship between the pathogenesis of cleft palate and the effects on MEE cells and palatal mesenchymal cells in rat embryos/fetuses exposed to TAC.

First observation of SiO2/Si(100) interfaces by spherical aberration-corrected high-resolution transmission electron microscopy.

SiO2/Si(100) interfaces were for the first time observed by a spherical aberration-corrected high-resolution transmission electron microscope in a cross-sectional mode. As the Fresnel fringes were not contrasted at the interfaces, the interfacial structures were clearly observed without the need for artificial image contrast. Atomic steps and defects on the Si(100) surfaces were accurately identified.