摘要:

AbstractAdult Sprague‐Dawley rats were fed diets containing 0, 0.25, 0.5, 1.0, or 2.0% of the food additive brominated vegetable (soybean) oil (BVO) for 2 weeks prior to mating. After conception, the diets were continued throughout gestation and lactation for the females. The same diets were also provided to the dams' offspring throughout their development (up to 90–120 days of age). BVO at 2.0% of the diet completely blocked reproduction. BVO at 1.0% of the diet severely impaired conception, reduced maternal body weight, and produced slightly reduced litter sizes but no evidence of malformations. At this dose postnatal mortality was high, and survivors showed impaired growth and severe behavioral impairments on a battery of standardized tests of functional development. After weaning, adequate data could not be obtained because of the high mortality rate in this group. BVO at 0.5% of the diet produced less reproductive interference and much less offspring mortality or impairment of growth, but produced behavioral impairments almost as severe as seen in the BVO 1.0% group. In addition, this group exhibited severely reduced postweaning activity, delayed vaginal patency development, and reduced day‐90 weight. BVO at 0.25% of the diet produced reproductive deficits similar to the BVO 0.5% group, but less severe effects on growth and behavioral development. This group showed no significant increase in offspring mortality. The data demonstrate clear evidence of dose‐related physical and behavioral developmental t

ISSN:0040-3709    

DOI:10.1002/tera.1420280302

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

年代:1983

数据来源: WILEY

摘要:

AbstractThe effects of perinatal exposure to phencyclidine (PCP) on the reflex development of the offspring of mothers given PCP during gestation and/or lactation were determined. ICR Swiss mice received daily injections of either PCP (5, 10, 20 mg/kg, PO) or saline during gestation and/or lactation. Thus, four groups of animals were studied; those exposed only prenatally, postnatally, both pre‐ and postnatally, or control. After birth, these offspring were observed daily until weaning for the appearance of certain reflexes, using a modification of the Fox battery. There was a delay in the disappearance of the cross extensor reflex and delayed appearance of reflexes, such as walking, crawling, vibrissal placement and vibrissal stroking in the offspring of PCP‐treated mothers. Treated animals also showed slower righting times than control animals. Growth rate was decreased in PCP‐exposed animals beginning at 3 days of age and continuing through 15 days of age. These results indicate that PCP exposure during gestation or nursing adversely affects the development of behavioral reflexes in mice and suggest that regular observation of reflex ontogeny in neonates may be a sensitive indicator of behavioral terat

ISSN:0040-3709    

DOI:10.1002/tera.1420280303

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

年代:1983

数据来源: WILEY

摘要:

AbstractThe cause of the embryopathy associated with diabetes mellitus is uncertain. To examine whether exogenously administered insulin may be teratogenic, tracer amounts of radiolabelled insulin were infused for two hours during organogenesis (day 12 1/2 of gestation) into three groups of pregnant rats: control (n = 8), diabetic (n = 5), and hyperinsulinemic (n = 4). For maternal plasma, no differences were found among the three study groups in the perecentage of the protein‐precipitable (insulin‐containing) radioactivity. Tissue radioactivities were expressed relative to the two‐hour maternal plasma sample. Maternal kidney samples had the highest total and protein precipitable counts followed in descending order by the maternal plasma, maternal liver, placenta, and embryo. No differences in radioactivities were noted among the three study groups for specific tissues studied. Protein‐precipitable radioactivities in the embryo were more than 100‐fold less than the maternal plasma values. In 11 of the 17 litters, the acid‐insoluble fractions of the embryos were not distinguishable from background counts, and none of the remaining six were greater than twice background. These studies demonstrate that during the period of organogenesis, the rat embryo is protected from maternal insulin by the placenta, and hence, maternal insulin in an unlikel

ISSN:0040-3709    

DOI:10.1002/tera.1420280304

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

年代:1983

数据来源: WILEY

摘要:

AbstractToxic effects of sodium selenite (SS) on dams and/or conceptuses and modification of the effects by vitamin E (VE) or reduced glutathione (GSH) were investigated in pregnant mice during late gestation. Dose‐dependent fetocidal effects and fetal growth retardation were observed in mothers injected SC with SS on day 12 but not on day 16 of gestation. On day 12, abortion occurred only at a dose level of 58.8 μmol/kg SS, whereas on day 16 it occurred at two dose levels: 27.2 and 40.0 μmol/kg SS. Pregnant mice were treated with or without VE (50 mg/kg, SC, daily from day 7 to day 11) and injected with a single dose of SS (46.2 μmol/kg, SC) on day 12. VE prevented abortion and maternal death, but none of the other effects such as fetal loss, fetal growth retardation, and decrease in body weight gain of the dams. Pretreatment with GSH (0, 2, or 5 mM/kg, SC) 20 min before SS injection on day 12 exacerbated maternal death, abortion, and decrease in body weight gain of the dams. No effect were observed in the number of live offspring, and in body weight of offsp

ISSN:0040-3709    

DOI:10.1002/tera.1420280305

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

年代:1983

数据来源: WILEY

摘要:

AbstractAdministration of single doses of retinoic acid to hamsters on days 7, 8, and 9 of pregnancy resulted in missing, irregular, and abnormally fused centers of ossification in the vertebrae of fetuses recovered near term. A study of early events in embryonic tissues following maternal treatment with 60 mg/kg of the teratogen on day 8 revealed a variety of changes which could be linked to the development of the bony defects. By 12 hours following treatment, the mean number of somites in teratogen‐exposed embryos was significantly reduced in comparison to controls. Within 24 hours of maternal treatment lesions were observed in the aortae of the retinoic acid‐exposed embryos. The vessels were consistently damaged caudally with dissection of aortic contents into the adjacent unsegmented mesoderm. Kinking of the neural tube, notochordal irregularities, and a loss of intercellular relationships in the paraxial mesoderm accompanied the vascular lesions. By 36 hours following treatment, abnormalities were evident in the appearance of the caudal somites, and at later stages these appeared to translate into defects in the sclerotomes and subsequently, the vertebrae. The observations suggest that vascular damage plays a significant role in the induction of the vertebral defects by disrupting somitogenesis. Moreover, the results support the hypothesis that retinoic acid produces abnormalities in the vertebral skeleton by a mechanism different from that which has been suggested to operate in the induction of defects in the limb skele

ISSN:0040-3709    

DOI:10.1002/tera.1420280306

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

年代:1983

数据来源: WILEY

摘要:

AbstractThe effect of dietary zinc and genetic strain on acetazolamide‐induced malformations was assessed. CBA (sensitive) and SWV (resistant) mice were fed purified diets containing five different levels of zinc throughout gestation and were given acetazolamide orally for a limited period during organogenesis. Controls received either no treatment or the drug vehicle. Litters were assessed for resorptions and malformations at term. The significance for influencing litter outcome was tested for the three main treatments: strain, dietary zinc level, and acetazolamide dose, plus their interactions. The magnitude of the litter response was strongly influenced by strain. The incidence of forelimb ectrodactyly, a characteristic malformation caused by acetazolamide, was much greater in CBA than in SWV fetuses. SWV fetuses had no ectrodactyly when dams were fed at least 9 μg/g zinc, but 5–8% showed ectrodactyly when dams received a zinc‐deficient (0.4 or 4.5 μg/g) diet. The incidence of ectrodactyly in the CBA strain decreased as dietary zinc increased, but was still present when dams were fed a high (1,000 μg/g) zinc diet. The incidence of resorptions and total abnormal sites from litters of dams receiving acetazolamide decreased as dietary zinc increased, with the magnitude of the response being influenced by the strain. A significant (dietary zinc × acetazolamide) and (strain × acetazolamide) interaction was found for the ectrodactyly response. The results demonstrate the importance of considering interactions among genetic strain, diet, and drugs, as well as single factors as determinants of

ISSN:0040-3709    

DOI:10.1002/tera.1420280307

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

年代:1983

数据来源: WILEY

摘要:

AbstractThe effect of the teratogen 2‐amino‐1,3,4‐thiadiazole on glycogenesis and glycogenolysis was investigated in the fetal and neonatal rat liver. At day 15, 16, or 17 of gestation (sperm day = day 0) pregnant Sprague‐Dawley rats received a single IP injection of an aqueous solution of aminothiadiazole. Dosages used were teratogenic (100 mg/kg maternal body weight) and nonteratogenic (10 mg/kg). At day 16 some rats received nicotinamide (100 mg/rat) in addition to a teratogenic dose of aminothiadiazole. Livers were recovered for assay at fetal day 20 and postnatal day 1. Only at day 16 did a teratogenic dose induce a significant depression in the fetal activity of glycogen synthetase (to 49.6% of control activity) and glucose‐6‐phosphatase (to 72.2% of control activity), and in glycogen accumulation (to 72.6% of control accumulation). At day 15, a teratogenic dose significantly depressed glucose‐6‐phosphatase activity but not glycogen synthetase activity or glycogen accumulation. Nicotinamide, given immediately after aminothiadiazole, was effective in blocking the inhibition. Teratogenic treatment had no effect on the postnatal activity of glucose‐6‐phosphatase. Apparently some event associated with birth releases the enzyme from its prenatal inhibition. These results demonstrate a parallelism between the perturbing effect of aminothiadiazole on biochemical development and morphological development with respect to time of insult, dose response, and protection with its antitertogen. The mechanism of action whereby aminothiadiazole depresses the activity of glycogen synthetase and glucose‐6‐phosphatase r

ISSN:0040-3709    

DOI:10.1002/tera.1420280308

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

年代:1983

数据来源: WILEY

摘要:

AbstractStudies comparing the methyl mercury (mHg) content of maternal and newborn blood have shown increased levels in the newborn. This has been attributed to facilitated transplacental diffusion because of high fetal hematocrit (Hct). This study shows the converse, that the diffusion of mHg diminishes progressively with increasing Hct. The diffusion of m203Hg across a Millipore membrane (0.45 μm) separating compartments A and B of a diffusion cell was studied. When both compartments contained saline or plasma alone, equilibration from A to B occurred in 5 h. Introduction of human red blood cells (RBC) in saline (Hct 20%) into B resulted in a twofold increase in diffusion of mHg when compared to saline alone. Increasing Hct in saline in compartment B resulted in a progressive decrease in diffusion (r = −0.95, P<0.001). The presence of RBC in plasma (Hct 20%) in B resulted in a 70% decrease in diffusion; with increasing Hct, diffusion was further reduced (r = −0.95, P<0.001). Direct addition of mHg to RBC in saline resulted in 98% RBC uptake. Increasing concentrations of plasma (at a constant Hct) resulted in a progressive decrease in RBC uptake. In undiluted plasma at Hct 14%, RBC uptake of mHg was 35%. Plasma electrophoresis showed that much of the mHg was associated with a high‐molecular‐weight lipoprotein fraction. Plasma components appear to be important in the distribution of mHg in blood, and may be a factor in the relatively higher blood levels in t

ISSN:0040-3709    

DOI:10.1002/tera.1420280309

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

年代:1983

数据来源: WILEY

摘要:

AbstractRecent studies have shown that phenytoin (Dilantin®) administration to pregnant A/J mice on day 10 causes reduced growth in embryonic primary palates. The current investigation concentrates on biochemical and autoradiographic changes toward the end of primary palate formation (gestational day 11), which coincides with the developmental period used for the previously conducted morphological studies. On gestational day 10, one group of pregnant A/J mice was injected intraperitoneally (IP) with 60 mg/kg phenytoin and the other group with vehicle. Twenty‐three hours after phenytoin administration, all animals were injected (IP) with either [3H]‐thymidine or [3H]‐leucine. After one hour of incorporation, animals were sacrificed, embryos removed and placed in ice‐cold Eagle's minimum essential medium containing 0.02% NaN3for biochemical assay or fixed immediately in Bouin's solution for autoradiography. For biochemical analyses, palates and limb buds were removed, homogenized, TCA precipitated, lyophilized, and acid hydrolyzed. Examination of the data revealed that DNA synthesis in control palates was 3.8‐fold greater than in primary palates from embryos of phenytoin‐treated mothers. Results were similar for limb buds from control embryos and from embryos of phenytoin‐treated mothers. Experiments utilizing [3H]‐leucine indicated that protein synthesis was 2.6‐fold greater in primary palates from phenytointreated mothers than in control primary palates. Similar results were obtained for protein synthesis in limb‐bud tissue from controls and embryos of phenytoin‐treated mothers. Autoradiographic data supported the biochemical findings. DNA synthesis in primary palates from embryos of phenytoin‐treated mothers decreased 3‐fold; protein synthesis increased 2.2‐fold compared with control primary palates. Similar autoradiographic results were obtained from limb‐bud tissue from embryos of phenytoin‐treated mothers. The results indicate that DNA synthesis is decreased and protein synthesis is increased in embryonic primary palates from phenytoin‐treated mothers. Similar changes in DNA and protein synthesis in embryonic limb buds indicate that phenytoin alterations

ISSN:0040-3709    

DOI:10.1002/tera.1420280310

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

年代:1983

数据来源: WILEY

摘要:

AbstractEarly tissue damage following a teratogenic dose of arsenic to the dam was studied in mice with the objective of detecting the primary lesion associated with the development of exencephaly. Animals were killed 6 to 21 h after a single 45 mg/kg intraperitoneal injection of sodium arsenate on day 8 of pregnancy and neurulation‐stage embryos were fixed for histological and ultrastructural examination. In the prospective hindbrain, the most consistent feature associated with arsenate treatment was the widely separated neural folds which were not positioned for closure. Intracytoplasmic inclusions, interpreted as necrotic debris, were most numerous in the apical portion of the neural folds, sometimes extending into the mesenchyme, but they were not extensive in most embryos. In the prospective forebrain, necrotic debris was found throughout the neuroepithelium, in contrast to the posterior portions of the developing brain. It is not clear that necrosis of the neuroepithelium or mesenchyme would in itself be the primary lesion associated with exencephaly, although death of specific cells such as those participating in the fusion process could be involved. The potential effect of arsenate on physiological and biochemical processes which could affect neural tube closure is discusse

ISSN:0040-3709    

DOI:10.1002/tera.1420280311

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

年代:1983

数据来源: WILEY