ISSN:0040-3709    

DOI:10.1002/tera.1420370302

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractPregnant Sprague‐Dawley rats received either 80 mg/kg d‐propoxyphene HCl or 20 mg/kg chlorpromazine HCl or 80,000 and 160,000 IU/kg vitamin A palmitate daily between the 6th and 20th days of gestation. Vehicle control groups were similarly treated with saline or corn oil and considered as negative controls. Offspring were examined for physical landmarks, neuromotor development, and behaviour using righting reflex, swimming, negative geotaxis, open field, rotarod, water maze, and nocturnal activity. This test battery included biochemical measurements. No reduction in parental weight and physical offspring development was observed. All these treatments produced long‐term changes in more than one test. Vitamin A palmitate (160,000 IU/kg) was judged as the best positive control with this test battery for future investigation of the behavioural teratology of

ISSN:0040-3709    

DOI:10.1002/tera.1420370303

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractA specific fetal disruption syndrome associated with maternal cocaine use has not as yet been documented. In the first 23 pregnancies evaluated in our program for chemically dependent women, one infant with prune belly syndrome and one infant with hypospadias were delivered to cocaine‐using women. In the present study, all infants delivered in our program received a renal ultrasound at 2–3 days of life. Fifty infants born to cocaine‐using women (group I) and 30 born to polydrug, noncocaine‐using women (group II) were evaluated. The two groups of women were similar for age, gravidity, and race. Mean birth weight of the infants in the two groups was similar. Seven infants in group I demonstrated genitourinary tract malformations while there were no infants with such malformations in group II. It is hypothesized that the vasoconstrictive effects of cocaine could explain the abnormalities of the genitourinary tract found in the cocaine‐expose

ISSN:0040-3709    

DOI:10.1002/tera.1420370304

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractTreatment of morula‐stage mouse embryos with mitomycin C (0.004–0.5 μg/ml) in vitro resulted in a decrease in the number of inner cell mass (ICM) cells at the blastocyst stage. The trophectoderm population was reduced only at the highest dosage (0.5 μg/ml) tested. Postblastocyst development in vitro was retarded: Fewer embryos formed trophoblastic outgrowth, and the ICM was poorly developed. The embryo transfer experiments demonstrated that a reduction in ICM cell numbers diminished the potential of embryogenesis. The presence of a sufficient number of trophoblasts and ICM cells in the blastocyst is therefore a prerequisite for successful implantation and embryogenesis. The mitomycin‐treated blastocysts with only 70% of normal ICM cells developed to egg cylinders that were about half normal size, but by days 12–14 the body size of the surviving embryo was similar to that of the control embryo. Morphogenesis was retarded during the early organogenesis stages, but only a slight delay was seen in the treated embryo on day 12. Such observation strongly suggests that a restorative phase of growth and morphogenesis has occurred during the immediate postimplantati

ISSN:0040-3709    

DOI:10.1002/tera.1420370305

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractWe report the results of studies on the reductive activation of the schistosomicidal agent, niridazole (NDZ). Intact rat embryos in vitro reduced this compound, generating a stable metabolite in the presence of 5% O2. By contrast, embryo and yolk sac homogenates or liver microsomes appeared to require anaerobiasis. Malformation incidence–specifically, axial asymmetry–showed a strong correlation with nitroreductase activity rates when the latter were modulated by oxygen tension.Data presented here suggest that when embryos are exposed to NDZ under conditions of low oxygen in vitro, redox cycling ensues with molecular oxygen serving to oxidize early reduction products. This process continues, regenerating the parent compound until oxygen is depleted locally. The basis of this localized depletion is unknown, but inability of the immature supply system to replete oxygen or demand by precociously aerobic tissues may be involved. Once local anaerobiasis is attained, further reduction could generate toxic metabolites capable of covalently binding cellular macromolecules. Localized hypoxia represents another potential mechanism of dysmorphogene

ISSN:0040-3709    

DOI:10.1002/tera.1420370306

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractThe relationships among microencephaly, peak blood alcohol concentration (BAC), and dose of alcohol were examined in a rat model of third‐trimester fetal alcohol effects. Ethyl alcohol was administered to neonatal rats from postnatal day 4 to day 10 during the brain growth spurt via an artificial rearing technique. Groups of rats received one of nine doses of alcohol (0.0, 2.5, 3.3, 4.0, 4.5, 5.3, 6.6, 7.5, or 8.5 g/kg body weight) administered in 8 hours each day. BACs were determined on postnatal days 6 and 7 at times corresponding to peak and trough BACs, respectively. On postnatal day 10, brains were removed, and total brain weights, cerebellar weights and brainstem weights were measured. Pups receiving 4.0 g/kg/day or less had mean peak BACs below 150 mg/dl and did not exhibit significant microencephaly when compared with controls. Higher dosages further increased the peak BAC and produced significant microencephaly. While a dose of 4.5 g/kg/day was sufficient to decrease significantly both total brain weight and cerebellar weight, a minimum dose of 6.6 g/kg/day was required for significant restriction of brainstem weight. The dose of 7.5 g/kg/day yielded a mean peak BAC of 420 mg/dl and reduced total brain weight, cerebellar weight, and brainstem weight by 33%, 52%, and 22%, respectively, relative to controls. Exposure to 8.5 g/kg/day was uniformly lethal. Peak BAC and total brain weight were highly correlated (r = −.916). As peak BAC increased, total brain weight decreased linearly. Comparisons with previous studies indicate that condensing the daily dose of alcohol effectively reduced the threshold doses for microencephaly and lethal

ISSN:0040-3709    

DOI:10.1002/tera.1420370307

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractPrenatal effects of acute maternal alcohol ingestion on chromosome segregation and mitotic frequency in the brain cells of the fetus were evaluated in mice by direct chromosome and mitotic counts and by flow cytometry. Fetuses were exposed to acute transplacental doses of alcohol for 4 days and killed on the fifth day. Those litters in which the fetuses were developed to the equivalent of normal 16th–17th‐day gestation age were analyzed. A marked increase in the number of hypoploid metaphases was observed in direct proportion to the dose ingested by the mother. An over 30% increase in hypoploidy over controls was measured in the fetuses exposed to the highest dose. Counts of mitotic cells showed an over tenfold increase in the mitotic index of the fetal brain exposed to alcohol. Flow cytometric measurements of DNA content in isolated fetal brain cell nuclei showed a shift from a single G0/G1peak in controls to a bimodal G0/G1– G2+M distribution in alcohol‐exposed fetuses of the same developmen

ISSN:0040-3709    

DOI:10.1002/tera.1420370308

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractThis study was done to determine the gestational period during which the rat fetus is susceptible to reduction of skeletal ossification by caffeine. Caffeine, 100 mg/kg/day by gavage, caused the greatest reduction in ossification, as assessed by staining with alizarin red S, in fetuses exposed between day 16 to 19 of gestation, less in those treated between day 7 to 19, and markedly less in those receiving it between day 7 to 16; a single dose on day 19 had very little effect. This indicates that the fetus is most susceptible late in pregnancy. Bones in early stages of mineralization on day 20 showed a greater reduction in staining than those in later stages. Thus, caffeine appears to lower the rate of ossification rather than reduce its final extent.In the day 7 to 19 caffeine treatment group, but not in the day 16 to 19 group, maternal and fetal body weights were reduced, and 1.6% of the fetuses had aphalangia. The day 7 to 16 caffeine treatment reduced fetal body weight. This argues against an association between reduction in fetal weight and ossification. None of the treatments affected rates of resorption or litter size.A novel and important observation made is that the different caffeine treatments affected the staining by alizarin of both claws and bones in a qualitatively and quantitatively similar manner. Since claws are devoid of osteoid, this observation questions the specificity of alizarin for the assessment of the state of fetal ossification and raises doubt as to the significance of the observed action of caffeine on ossification.

ISSN:0040-3709    

DOI:10.1002/tera.1420370309

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractThe relationship between maternal aspirin use during the first 20 weeks of pregnancy and the child's IQ at 4 years of age was investigated in 19,226 pregnancies occurring from 1959 to 1966 in the Collaborative Perinatal Project. The mean IQ of children exposed to aspirin was 98.3, which was 2.1 points higher (95% confidence interval = 1.7, 2.6;P<0.0001) than that of unexposed children. Adjustment for multiple social, demographic, and other confounders reduced this difference to less than one point in favor of the aspirin exposed group, although statistical significance remained. Total days of exposure was used as an index of dose, and no dose‐response relationship between aspirin use and IQ was found. The effect of prenatal aspirin exposure did not vary by infant sex. It is concluded that an adverse effect of aspirin exposure on IQ is unlikel

ISSN:0040-3709    

DOI:10.1002/tera.1420370310

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractPregnant ICR mice were treated with single whole‐body X‐radiation at a dose of 0.24 Gy on day 10, 13, or 15 of gestation. Fetuses were obtained from mothers during 1 and 24 hours after irradiation. Pyknotic cells in the ventricular zone of telencephalon were counted in serial histological sections. Incidence of pyknotic cells peaked during 6 and 9 hours after irradiation in each gestation day group. Then, dose‐response curves were obtained 6 hours after 0–0.48 Gy of irradiation. All three dose‐response curves showed clear linearity in the dose range lower than 0.24 Gy. Ratios of radiosensitivity estimated from the slopes of dose‐response curves in day 10, 13, and 15 groups were 1, 1.4, and 0.4, respectively. These demonstrated that ventricular cells in the day 13 fetal telencephalon were the most radiosensitive among the three different age groups.In order to confirm the presence of the highly radiosensitive stage common to mammalian cerebral cortical histogenesis, pregnant F344 rats were treated with single whole‐body γ‐irradiation at a dose of 0.48 Gy on day 13, 14, 15, 17, or 19 of gestation. The incidence of pyknotic cells in the ventricular zone of telencephalon was examined microscopically during 1 and 24 hours after irradiation. The peak incidence was shown 6 hours after irradiation in all the treated groups, and the highest peak incidence was shown in day‐15‐treated group. The developmental stage of telencephalon of day 15 rat fetuses was comparable to that of day 13 mouse fetuses. Thus, the highest radiosensitivity in terms of acute cell death was shown in the same developmental stage of brain development, i.e., the beginning phase of cerebral cortical histogenesis, i

ISSN:0040-3709    

DOI:10.1002/tera.1420370311

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY