摘要:

AbstractThe teratogenic and postnatal developmental effects of morphine exposure during pregnancy were studied in Sprague‐Dawley rats in three separate experiments using chronically implanted osmotic minipumps in order to avoid respiratory depression. In the first experiment, the teratogenic effects of three different morphine dosages were studied: a low dose (10 mg/kg/day), an intermediate dose (35 mg/kg/day), and a high dose (70 mg/kg/ day). On day 5 of gestation, osmotic minipumps that deliver their contents at a constant rate for 15 days were implanted subcutaneously on the back of the rats. On day 20 of gestation, cesarean sections were performed, reproductive indices were determined, and fetuses were examined externally and then preserved for subsequent visceral and skeletal examinations. The pregnancy rate was significantly reduced at the intermediate and high doses to 57% and 6%, respectively (control, 83%). No teratogenic effects were observed at any dosage, but growth retardation was present in the intermediate‐dose group. In the second experiment, postnatal survival of the offspring of dams treated with either normal saline, morphine (35 mg/kg/day); or the synthetic opioid, fentanyl (500 μg/kg/day) were studied. Offspring of morphine‐treated dams had a significantly higher mortality rate, which peaked at 56% within 2 days. No effect was seen after fentanyl treatment. In the third experiment, pups of morphine‐treated dams were cross‐fostered by saline‐treated dams; the postnatal mortality in offspring of morphine‐treated dams remained high (62%). Our results indicate that doses of morphine up to 35 mg/kg/day delivered by osmotic minipumps are not teratogenic in rats but cause other adverse fetal effects that result in increased postn

ISSN:0040-3709    

DOI:10.1002/tera.1420380502

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

年代:1988

数据来源: WILEY

摘要:

AbstractThis study was part of a multidisciplinary investigation of the effects of gestational ethanol exposure in nonhuman primates. Thirty‐one pregnantMacaca nemestrinawere exposed to weekly ethanol doses of 0.0, 0.3, 0.6, 1.2, 1.8, 2.5, 3.3, or 4.1 g/kg maternal weight. Dose cohorts 0.0 through 1.8 were exposed to the initial ethanol dose within 10 days postconception. Dose cohorts 2.5 through 4.1 received their initial dose after the fifth week of gestation. Morphometric analyses performed on cranial radiographs showed that animals exposed to high doses of gestational ethanol had, on average, slightly smaller, distorted crania than control animals. A dysmorphic, flat face characteristic of fetal alcohol syndrome was recognized in one animal of the 1.8 g/kg cohort. The animal that received the highest doses of gestational ethanol was microcephalic. Similar malformations were not seen with low ethanol exposures or in controls. These data suggest a pattern of cranial distortion that may be recognizable and characteristic of ethanol teratogenesi

ISSN:0040-3709    

DOI:10.1002/tera.1420380503

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

年代:1988

数据来源: WILEY

摘要:

AbstractDimethylsulfoxide (DMSO) is known to antagonize the teratogenic effects of secalonic acid D (SAD) in mice. To establish the optimum protective dose of DMSO, pregnant CD‐1 mice were treated, i.p., with 30 mg/kg of SAD in 5% (w/v) NaHCO3, containing 0, 10, 20, or 30% (v/v) DMSO on day 11 of gestation. Data indicate that at 10% and 20% levels, DMSO affords an apparent dose‐related protection against SAD‐induced cleft palate, whereas 30% DMSO enhanced fetal resorption with no reduction in the incidence of cleft palate. Ultraviolet spectra and TLC mobility indicated that DMSO at 20% did not directly interact with SAD. Distribution and elimination of14C‐SAD was studied in fetal and maternal tissues from pregnant mice at 24 and 48 hr after exposure to 30 mg/kg of14C‐SAD, i.p., in NaHCO3(control) or in 20% DMSO. Compared with those not receiving DMSO, maternal exposure to DMSO: (1) significantly reduced (42–75%) radioactivity in fetal heads and bodies, placenta, and maternal tissues other than liver; (2) significantly increased (up to 222%) the radioactivity in maternal liver; and (3) significantly reduced (44–58%) fecal and urinary elimination of SAD‐derived radioactivity. These results suggest that the antiteratogenic effect of DMSO against SAD may be at least partly mediated by increased SAD (or its metabolites) retention by maternal liver leading to reduced SAD upta

ISSN:0040-3709    

DOI:10.1002/tera.1420380504

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

年代:1988

数据来源: WILEY

摘要:

AbstractThe proportion of children born with a particular defect is not a “birth defect rate” but, rather, a prevalence proportion. The implications of confusing a rate and a proportion are discussed in terms of the interpretation of birth defect data. It is recommended that “prevalence proportion” or “prevalence” be used to report the frequency of various defects rather than the often‐used “p

ISSN:0040-3709    

DOI:10.1002/tera.1420380505

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

年代:1988

数据来源: WILEY

摘要:

AbstractThirty‐nine pregnant adult Wistar strain rats were randomly assigned to one of three exposure groups: 0, 0.75, or 1.50 Gy X‐radiation total exposure. Animals were exposed from the 14th to the 18th days of gestation at 0, 0.15, or 0.30 Gy per day. At term, 15 rats were killed and morphologic analyses were completed. Twenty‐four rats were allowed to deliver their offspring. On the first day of postnatal life, litters were reduced to a maximum of eight pups per litter, with equal numbers of male and female offspring wherever possible. A total of 187 pups were observed for the age of acquisition of five reflexes (air righting, surface righting, visual placing, negative geotaxis, auditory startle) and the appearance of four physiologic markers (pinna detachment, eye opening, vaginal opening, testes descent). There was significant dose‐related weight reduction in term fetuses and offspring throughout the 86‐day postnatal period. Postnatal growth rate (g gained/day) was unaffected. Adult offspring brain and gonadal weight and organ weight:body weight ratios were reduced. Using the PAC50 methodology, dose‐related alterations occurred in the acquisition of several reflexes. All physiologic markers exhibited a dose‐related delay in appearance. These results indicate that fractionated exposure to X‐radiation during the fetal period in the rat results in dose‐dependent alterations in postnatal growth and physiologic development. These studies are important for our understanding of the long‐range effects of prenatal exposure to ionizing radiatio

ISSN:0040-3709    

DOI:10.1002/tera.1420380506

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

年代:1988

数据来源: WILEY

摘要:

AbstractIt is evident that significant permanent tissue hypoplasia can be produced following radiation exposure late in fetal development. Because two organs, brain and testes, are developmentally and functionally interrelated, it was of interest to determine whether fetal testicular hypoplasia was a primary or a secondary effect of fetal brain irradiation. Twenty‐four pregnant Wistar strain rats were randomly assigned to one of four groups, and a laparotomy was performed on day 18 of gestation. The fetuses received sham irradiation, whole body irradiation, or only head/thorax or pelvic body irradiation at a dosage level of 1.5 Gy. Mothers were allowed to deliver and raise their offspring until postnatal day 30, when the offspring were weaned. At 60 days of age, 74 male offspring were allowed to mate with colony control females of similar age until successful insemination or until the males reached 90 days of age, when they were killed. Testes were weighed and processed for histologic examination. Direct radiation of testes, due to whole body or pelvic exposure, resulted in testicular growth retardation and significantly reduced spermatogenesis. Breeding activity of the males and the percent of positive inseminations were also slightly reduced. However, a significant percentage of male offspring receiving direct testicular radiation did produce offspring. Head/thorax‐only irradiation did not adversely affect testicular growth or spermatogenesis. Therefore, the use of histologic analysis as the sole determinant of infertility may be misleading. This study indicates that testicular growth retardation and an increased infertility rate result from direct prenatal exposure of rat testes to X‐radiation and are not necessarily mediated via X‐irradiation effects on the central nervous

ISSN:0040-3709    

DOI:10.1002/tera.1420380507

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

年代:1988

数据来源: WILEY

摘要:

AbstractA clinical, radiological, and morphological study of a congenital occipito‐atlanto‐axial malformation in a 13‐week‐old male Saint Bernard dog that became suddenly tetraplegic at 8 weeks is described. The dog was recumbent, had generalized muscle atrophy, but was alert and responsive. Pain was elicited when the head‐neck junction and the cervical vertebrae were palpated, and a bony abnormality was palpated at the occiput and atlas. Clinical signs of upper motor neuron and general proprioceptive deficits in all four limbs were compatible with a focal lesion in the cervical spinal cord. Plain radiographs of the head and neck revealed malformation of the occipital bones, atlas, and axis, unilateral atlanto‐occipital fusion, and atlanto‐axial sub‐luxation. At necropsy the right half of the atlantal neural arch was fused to the right exoccipital bone. On the axis, the dens was small, malformed, and deviated to the left; the transverse processes were enlarged; and the spinous process was small with a cleft caudally. The spinal cord was severely compressed at the level of the atlanto‐axial articulation, and histological examination revealed extensive loss of neuronal cell bodies, axons, myelin, and the central canal. Reactive astrogliosis was also extensive. After a discussion of normal and abnormal development of the vertebral column and its joints, it was concluded that a failure of normal joint development at about 30 days of gestation in the dog could lead to congenital occipito‐atlanto

ISSN:0040-3709    

DOI:10.1002/tera.1420380508

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

年代:1988

数据来源: WILEY

摘要:

AbstractA teratological assessment was performed using rats that were exposed to an alternating magnetic field. The magnetic field had a sawtooth waveform similar to that produced by video display terminals (VDTs). Female rats were exposed 2 weeks prior to and throughout pregnancy at a rate of 7 h/day. Three intensities of magnetic field (5.7, 23 or 66 μT) were used. All of these field intensities were much greater than those to which VDT users are exposed. A slight but statistically significant decrease in maternal lymphocyte count for the highest intensity field was found as compared with the control group. However, the lymphocyte count was within the normal range, and the observed changes in hematological parameters were considered mild. No other maternal or fetal parameters that were examined showed a significant difference for any of the three field intensities. Where minor variations in skeleton, development were observed they were known to be the common “noise” that appears in every teratological evalua

ISSN:0040-3709    

DOI:10.1002/tera.1420380509

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

年代:1988

数据来源: WILEY

摘要:

AbstractVitrification of mouse oocytes adversely affected the subsequent developmental potential of embryos and fetuses derived from the fertilization of such oocytes after thawing. Only 5% of oocytes vitrified formed viable fetuses on the 15th day of gestation as compared to 47% in the controls. The incidence of chromosomally aneuploid zygotes, derived from cryopreserved oocytes, was approximately threefold higher than the controls irrespective of whether the oocytes were cryopreserved by vitrification or DMSO slow‐freezing. Malformed fetuses were obtained from oocytes that had been vitrified as well as those that had been exposed to vitrification solutions only, whereas no malformed fetuses were obtained in oocytes slow‐frozen by DMSO or fresh controls–thus demonstrating that the exposure of oocytes to the vitrification chemicals was responsible for the fetal malformations. The data in this study suggest that the vitrification technique should be cautiously applied to human oocyte cryopreservation. Furthermore', the data also demonstrate that the exposure of female gametes to carcinogenic and/or teratogenic chemicals may result in malformed embryos when such oocytes are subsequently ferti

ISSN:0040-3709    

DOI:10.1002/tera.1420380510

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

年代:1988

数据来源: WILEY

摘要:

AbstractThe autosomal mutationbrachypod(bpH/bpH) in the mouse affects the development of precartilage mesenchymal condensation in the limb‐bud. We have previously shown that this defect is localized to the expression of terminal N‐acetylglucosamine (GlcNAc) glycoproteins in the plasma membrane (Elmer and Wright, '83). The present study is focused on cell surface galactosyltransferase (GalTase), an ectoenzyme that transfers galactose to its GlcNAc substrate. Purified plasma membrane preparations derived from wild‐type ( +/+ ), heterozygote (+ /bpH) andbrachypod(bpH/bpH) embryonic mouse limb cells were assayed for GalTase activity during in vitro and in utero chondrogenesis using High‐Performance Liquid Chromatography (HPLC). On embryonic day E12, prior to overt expression of the mutant gene, no significant difference in GalTase activity was observed. By the third day in culture, all major chondrogenic elements of the autopod were present in +/+ and +/bpHembryos, whereas the mutant autopods were markedly deficient in staining and appeared consistently shorter. The accumulation of alcianophilic cartilage matrix in the wild‐type was accompanied by a 29% increase in GalTase activity, which reflected the net change (29%) observed during development from days E12 to E13 in utero. The GalTase activity for the in utero E13 mutant (13%) was significantly different from control. In culture, day E12 mutant autopods actually decreased in their GalTase level by 3 days so that the activity was reduced to only 57% of the wild‐type. Though GalTase activity in the heterozygote showed an intermediate expression, optical image analysis did not reveal consistent differences in cartilage development when compared to +/+, arguing against a gene‐dosage effect at the gross anatomical level. These data indicate that an increase in plasma membrane GalTase activity is a natural developmental event that occurs during limb‐bud chondrogenesis and a decrease in GalTase activity contributes to the dysmorphogenesis inbra

ISSN:0040-3709    

DOI:10.1002/tera.1420380511

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

年代:1988

数据来源: WILEY