5-Bromo-2'-deoxyuridine (BrdU) was administered intraperitoneally to Sprague-Dawley rats at doses of 12.5, 25, 50, or 100 mg/kg/d on days 9 through 15 of gestation, and at 50 or 100 mg/kg/d on days 16 through 20 of gestation. Dams were allowed to deliver naturally and the numbers of live and dead pups were recorded. Male offspring were allowed to mature and then cohabited with untreated female rats for assessment of reproductive performance. Dam body weight gain during pregnancy and lactation periods was not reduced by the treatment with BrdU. Dams treated with 50 and 100 mg BrdU/kg on days 9 through 15 of gestation had litters with decreased survival rates. The male offspring from dams treated with 25, 50, and 100 mg BrdU/kg on days 9 through 15 of gestation had reduced body weights over the course of the entire study. A dose-related decrease in copulation and fertility rates was found in the male offspring of dams treated on days 9 through 15 of gestation, while no significant decrease in those rates were found in the male offspring of dams treated on days 16 through 20 of gestation. Neither histopathologic examination of testes nor sperm examination indicated the cause of the impaired fertility in the male offspring from dams treated with BrdU on days 9 through 15 of gestation. All of the male offspring of dams treated with 100 mg BrdU/kg on days 9 through 15 of gestation failed to copulate, and some of the male offspring of dams treated with 50 mg BrdU/kg on days 9 through 15 of gestation did not form copulatory plugs or formed very small plugs. Dilatation of the lateral ventricles and cysts in the pars distalis of the pituitary were observed in all of the male offspring of dams treated with 100 mg BrdU/kg on days 9 through 15 of gestation. The impaired fertility of the male offspring of dams treated prenatally with BrdU may have resulted from BrdU exposure effects on central nervous system action such as loss of libido and from failure to form proper copulatory plugs, rather than the direct effects of BrdU on the male reproductive organs.

Animals↗

PubMedDate not supplied

Growth and behavioral changes in mice prenatally exposed to methylmercury and heat.

Postnatal and behavioral changes in mice exposed prenatally to methylmercury and heat were investigated. Pregnant ICR mice were immersed in water at 37 degrees C or 42 degrees C for 10 min once or twice daily from day 12 through day 15 of gestation. Two hours after the heat exposure on day 12 of age, mice were injected s.c. with 5 mg Hg/kg of methylmercury (MeHg, as chloride) or saline. Prenatal exposure to heat significantly induced inactivity in an open field test (OPF) in males and retarded walking ability in both males and females. Prenatal exposure to MeHg caused significant inactivity in the OPF in females. Although heat did not enhance the effect of MeHg on physical growth or the behavior of pups and vice versa, there were some interactions between the effects of these two agents. Thus, the difference in walking ability in both sexes caused by heat was more distinctive in the saline-treated groups than in the MeHg-treated groups; the difference in locomotion in OPF caused by MeHg in females was more distinctive in the normothermic group than among the hyperthermic groups. The mechanisms underlying these behavioral changes need to be further examined.

Analysis of Variance↗

PubMedDate not supplied

In utero exposure to methylmercury and Se deficiency converge on the neurobehavioral outcome in mice.

Pregnant female ICR mice, maintained on torula-based diets containing various amounts of Se (0.02, 0.05, or 0.4 mg/kg diet), were given methyl-mercury (MeHg; 0, 5, or 9 mg Hg/kg in total) on the 12-14th days of gestation. The neurobehavioral function of the offspring born to these dams was evaluated with respect to reflex and motor development, thermal preference, and open-field activity. Se deficiency per se as well as exposure to MeHg exerted additive or synergistic effects on the neurobehavioral functions examined. The group of mice most affected was the group given the lowest amount of Se and the highest dose of MeHg. Thus, the neurobehavioral outcome of in utero MeHg exposure and Se deficiency converged. Although the dietary level of Se did not affect the Hg concentration in the fetal brain, the Se concentration and the activity of glutathione peroxidase, a selenoenzyme, were severely depressed by MeHg in the neural tissue. The possibility that functional Se deficiency by MeHg exposure partly accounts for the neurobehavioral toxicity of MeHg is discussed.

Animals↗

PubMedDate not supplied

Differential effects of yohimbine, naloxone and 8-OH-DPAT on ejaculatory response in male dogs.

The aim of this study was to compare the effects of the alpha(2)-adrenergic-receptor antagonist yohimbine, the 5-HT(lA)-receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and the opioid-receptor antagonist naloxone (all of which have been shown to stimulate male sexual arousal/motivation in rats) on sexual responses in male dogs. Sexual responses (i.e., ejaculation, penile erection and pelvic thrusting behavior) were elicited by manual penile stimulation. Systemic administration of yohimbine (0.03-1.0 mg/kg) produced a biphasic dose response curve for the amount of ejaculated semen collected during genital stimulation (for 5 min), whereas 8-OH-DPAT (0.03-0.3 mg/kg) dose-dependently decreased the amount of ejaculated semen. Thus, yohimbine increased the amount of ejaculated semen at lower doses (0.03-0.3 mg/kg), but decreased it at the highest dose (1.0 mg/kg). The highest dose of yohimbine (1.0 mg/kg) and 8-OH-DPAT (0.3 mg/kg) also produced a significant delay of onset in both ejaculation and penile erection latency (time from starting the stimulation to the first ejaculation and full erection), and a decrease in the incidence of pelvic thrusting behavior. In contrast, administration of naloxone (0.03-1.0 mg/kg) did not affect the sexual responses elicited by genital stimulation. These results indicate that yohimbine and 8-OH-DPAT, but not naloxone, affect sexual responses, particularly ejaculation, and that the drugs which stimulate the mechanisms regulating sexual arousal/motivation in male rats do not show identical effects for sexual function in male dogs. The present findings also confirm our previous observations that the ejaculatory capacity in dogs can be stimulated by lower doses of yohimbine, as evidenced by an increase in the amount of ejaculated semen.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMedDate not supplied

Gallyas- and tau-positive glial structures in motor neuron disease with dementia.

We have studied Gallyas- and tau-positive glial structures in three autopsied cases of motor neuron disease with dementia (MND-D). Gallyas-positive, tau-immunoreactive thread-like structures in the neuropil and crescent/coiled inclusions in the glial cells were mainly observed in the hippocampus, parahippocampal gyrus, and amygdaloid nucleus. Double staining using Gallyas staining and carbonic anhydrase 2 (CA2) immunohistochemistry revealed that some crescent/coiled inclusions occurred in the CA2-immunopositive cytoplasm of the oligodendroglia. Electron microscopic study with the Gallyas-Braak method revealed that the inclusion was a reticular, partly compact mass, containing 15 nm fibrils around round or oval nuclei. Since the regions where these structures appeared exhibited neuronal loss with gliosis, these data suggest that a cytoskeletal abnormality involving tau protein in glia might be associated with the degenerative process of MND-D.

Aged↗

PubMedDate not supplied

The micronucleus test of benzo[a]pyrene with mouse and rat peripheral blood reticulocytes.

The micronucleus test using peripheral blood reticulocytes (RETs) was evaluated in CD-1 and BDF1 mice and Sprague-Dawley rats treated with benzo[a]pyrene at two independent laboratories. The maximum incidence of micronucleated reticulocytes (MNRETs) appeared in both strains of mice 48 h after the treatment; interlaboratory differences were small. The incidence of MNRETs in BDF1 mice was higher than in CD-1 mice. In rats, significant increases of MNRETs with the maximum response at 72 h were detected when B[a]P was administered i.p.; slight but significant increases were observed at 24 h or later, with the maximum at 24-48 h, when it was administered p.o. These results suggest that the new method for the micronucleus test using circulating RETs will be useful in the detection of the clastogenicity of chemicals.

Animals↗