摘要:

AbstractEflornithine hydrochloride (DFMO) is a highly selective, enzyme‐activated, irreversible inhibitor of the enzyme L‐ornithine decarboxylase (ODC). Because of its role in the biosynthetic pathway of polyamines, ODC is essential for the growth and development of newly implanted embryonic tissue. In order to assess its effect on embryonic growth and fetal development, at various stages of gestation, DFMO was administered in the drinking water to pregnant rats and rabbits at several concentrations (from 0.03% to 3.0%) and times (from days 7, 10, or 11 through days 18 or 19). Rats were killed on day 21 and rabbits on day 29 of pregnancy (day 1 = day of insemination), and the implantations and fetuses were examined. At a concentration of 1.0% (approximately 1,270 mg/kg/day) in rats and 3.0% (approximately 915 mg/kg/day) in rabbits, maternal food and water consumption and body weight gain were significantly reduced during the treatment period, and all implantations were aborted or resorbed. At lower doses (approximately 200–600 mg/kg/day) fetuses survived to term, though in reduced numbers, and a marked reduction in average fetal weight was seen. At levels of 60 mg/kg/day or lower, there were no deleterious effects to the dams or their offspring. Few malformations were detected at any dose level by gross teratologic examination; nor were any considered to have been drug induced because of their sporadic incidence. The embryotoxicity and severe growth retardation demonstrated by these studies verify that adequate polyamine levels are essential for normal embryonic and fetal develo

ISSN:0040-3709    

DOI:10.1002/tera.1420390202

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

年代:1989

数据来源: WILEY

摘要:

AbstractUsing the autoradiographic technique of percent labeled mitoses (PLM), total cell cycle length (Tc) and lenght of the cell cycle phases G1, S, G2, and M have been estimated for the neuroepithelium and heart of day 10 rat embryos. The Tc for the neuroepithelium was estimated to be 9.45 hr, consisting of G1of 1.24 hr, S of 6.15 hr, G2of 1.34 hr, and M of 0.72 hr. The Tc for the heart was estimated to be 13.37 hr, consisting of G1of 4.30 hr, S of 7.01 hr, G2of 1.81 hr, and M of 0.25 hr. Comparison of cell cycle parameters in these two tissues indicates that the longer cell cycle in heart tissue is related primarily to an increase in G1. If embryos are exposed to the major teratogenic metabolite of cyclophosphamide, phosphoramide mustard, cell cycle analysis reveals that the S phase of the neuroepithelial cell cycle is lengthened and cells are either slowed or arrested in G2.

ISSN:0040-3709    

DOI:10.1002/tera.1420390203

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

年代:1989

数据来源: WILEY

摘要:

AbstractSerum, but not epidermal growth factor (EGF), stimulated the release of radiolabeled inositol phosphates from human embryo palate mesenchyme (HEPM) cells prelabeled with [3H]‐myoinositol. Pretreatment of cells with 10−6M dexamethasone (DEX) for 48 h had no effect on the release of inositol phosphates in response to serum. Furthermore, although treatment of the glucocorticoid‐sensitive A/J strain of mouse embryo palate mesenchyme (MEPM) cells with 10−6M DEX inhibited their proliferation by 40%, it had no effect on the activity of phospholipase(s) C. However, DEX did enhance the incorporation of [3H]‐myoinositol into membrane lipids. We interpret these data to mean that 1) serum factors enhance metabolism of inositol lipids in HEPM cells, 2) DEX does not interfere with the primary events by which agonists utilize metabolism of inositol lipids as a mechanism for transmembrane signaling, and 3) DEX may affect synthesis of phosphoinositides, as reported by Grove et al. (Biochem. Biophys. Res. Commun. 110:200–207, 1983; J. Craniofac. Genet. Dev. Biol. Suppl. 2:285

ISSN:0040-3709    

DOI:10.1002/tera.1420390204

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

年代:1989

数据来源: WILEY

摘要:

AbstractLimb reduction defects occurring among 1,213,913 consecutive livebirths in British Columbia during the period 1952–1984 inclusive were reviewed. A total of 659 cases of limb reduction defects were identified, 393 of them involving the long bones and 190 of them more than one limb. The time period 1966–1984, during which ascertainment was consistent, was evaluated, and an incidence of 5.97 per 10,000 livebirths (1 in 1,692 live births) was found. The data were evaluated for trends over time, sex ratio, and regional and ethnic distribution. Associated anomalies of other organ systems in these cases were analyzed, and overall about one‐half of the cases have additional defects. The majority of these additional defects affect the musculoskeletal system and include such entities as clubfoot, hip dislocation, and congenital contractures. Defects are also frequent in other organ systems, such as the cardiovascular, gastrointestinal, and genitourinary systems. By far the most common limb defects are terminal longitudinal defects then terminal transverse defects. Of all cases of limb defects, 75% are upper limb and 25% lower limb. We found no evidence that one side is affected more frequently.About 6.5% of cases had another family member registered with a skeletal defect; 12.9% of cases died within the first year of life, the majority (85%) of those dying having additional defects. Etiological considerations are discussed for some subgroups. A classification system for limb defects suitable for use by registries using the World Health Organization (WHO) International Classification Disease (ICD) 9th Revision is desc

ISSN:0040-3709    

DOI:10.1002/tera.1420390205

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

年代:1989

数据来源: WILEY

摘要:

AbstractThe frequency of use of ultrasonography for evaluating the developing embryo/fetus has continued to rise although the possible risks from exposure still remain uncertain. The cynomolgus macaque (Macaca fascicularis) is currently being used in our laboratory as a model to assess these risks. In utero exposure was performed utilizing a commercial real‐time mechanical sector scanner with a 7.5 MHz scanhead (ATL, MK 600). Maximum acoustic power output for this unit is as follows: I(SPTA) = 12.0 mW/cm2, I(SPPA) = 98 W/cm2, and Im= 137 W/cm2. Animals exposed to ultrasound (N = 16) were scanned five times weekly on gestational days (GD) 21–35±2 for 10 minutes/exam (m/e), three times weekly on GD 36–60±2 for 10 m/e, and once weekly on GD 61–150±2 for 20 m/e. Controls (N = 14) were “scanned” with the unit placed onstandby. Assessment of simian Apgar scores at 1, 5, and 10 minutes of life revealed higher scores for treated animals at 10 minutes (P⩽0.045); greater scores in muscle tone (P±0.013) and color (P±0.016) were observed. Evaluation of morphometrics at birth including weight, biparietal diameter, occipitofrontal diameter, head circumference, hand and foot lengths, humerus and femur lengths, arm circumference, chest circumference, tail length, skinfold thickness, and crown‐rump length (CRL) indicated a significant reduction in only two parameters, birth weight (P±0.027) and CRL (P±0.033). Hematologic analysis at 2±1, 9±1, and 16±1 days of life revealed a significant difference in white blood cell counts (WBCs). Treated animals displayed lower WBCs with reductions in numbers of segmented neutrophils and monocytes at all ages observed. Hematologic differences were not significant by 5–6 months of age. No abortions, gross malformations, or stillbirths were obse

ISSN:0040-3709    

DOI:10.1002/tera.1420390206

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

年代:1989

数据来源: WILEY

摘要:

AbstractThe extensive use of ultrasonography for the prenatal assessment of growth and development continues to present questions regarding biological effects. We are currently evaluating a nonhuman primate model(Macaca fascicularis)exposed to ultrasound from gestational day (GD) 21 to 152 ± 2. Exposures were performed with a commercial real‐time sector scanner (ATL, MK 600); animals were scanned five times weekly on GD 21–35 ± 2, three times weekly on GD 36–60 ± 2, and once weekly on GD 61–150 ± 2. The length of exposure was approximately the same as human exposure (GD 21–60 ± 2 = 10 min/exam and GD 61–150 ± 2 = 20 min/exam) although the frequency of the examinations was considerably greater. Initial reports indicated differences between control and treated animals including lower birth weight, higher simian Apgar scores, and changes in select hematologic parameters. Follow‐up evaluations of growth during the first year included measurements of body weight, hand and foot lengths, humerus and femur lengths, biparietal and occipitofrontal diameters, head circumference, arm circumference, chest circumference, skinfold thickness, and crown‐rump length. Results indicated a significant reduction in body weight in treated animals during the first three months, with nonsignificant differences during the following nine months. Hematologic analysis including complete blood counts (CBC) and clinical biochemistry at 6, 9, and 12 months of age were not significantly different. A series of behavioral evaluations including a neurobehavioral test battery (NBT) and tests assessing motor and cognitive skills were included. The NBT revealed increased muscle tone in treated animals at one, two, and four days. In an observation cage (week 1–14) more quiet activities were displayed by treated animals. Group differences in performance of motor and cognitive tasks were observed and may be attributable to agitation and difficulties in adjusting to test environments. There were no group differences observed in discrimination learning. When considering the possible implications to the human population, it is important to consider the amount of exposure these animals received, and the fact that most of the effects observed appeared to be transitory. Although human epidemiological studies have not revealed any significant bioeffects, the “prudent use” of diagnostic ultrasound should still be kept in mind. This is especially significant with the current rise in the use of endovaginal

ISSN:0040-3709    

DOI:10.1002/tera.1420390207

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

年代:1989

数据来源: WILEY

摘要:

AbstractThe present study investigated microscopically the process of 5‐azacytidine (5‐AC)‐induced digital teratogenesis and caffeine's suppressive effect on this process. Three distinct zones of programmed cell death were observed in control and caffeine‐treated embryos 3 hours after 5‐AC injection: the preaxial and postaxial ectodermal regions and the central part of the mesodermal regions. 5‐AC temporarily suppressed programmed cell death in the ectoderm and mesoderm 3 hours after it was injected. However, caffeine promoted programmed cell death; normal programmed cell death was observed in the limb buds of embryos whose dams were treated with 5‐AC and caffeine. The percentage of total cell death in hindlimb buds of embryos treated with 5‐AC and caffeine was higher than that from embryos treated with 5‐AC, whereas 5‐AC‐induced digital malformations were reduced by post‐treatment with caffeine. Cell death reached a maximum 12 hours after the injection in limb buds from 5‐AC and caffeine‐treated embryos and at 24 hours in the 5‐AC treated embryos. Furthermore, in the 5‐AC and caffeine‐treated embryos, the frequency of cell deaths at 12 hours increased almost linearly with the doses of caffeine in parallel with the reduction of 5‐AC‐induced malformation frequency by caffeine. These results suggest that although induced cell death may be one of the factors leading to digital malformations produced by 5‐AC, it is not essential, and the existence of other factors affecting the patter

ISSN:0040-3709    

DOI:10.1002/tera.1420390208

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

年代:1989

数据来源: WILEY

摘要:

AbstractOn embryonic day 21, pregnant guinea pigs were exposed to a 44°C environment for 1 hour. As a result, all brain ventricular zone cells in M phase of the mitotic cycle when heat‐shock occurred became immediately pyknotic and all cell division was stopped for 4–8 hr. The pyknotic cells were removed at a definable rate until mitosis resumed, after which removal occurred in an apparently random manner. Long delays in the return to mitosis were related to increased destruction of S‐phase cells deep within the ventricular zone and largely confined to the alar lamina. Upon recovery, a rostrocaudal delay in mitosis was apparent, and the number of mitotic figures was increased compared with control numbers for 1 hr, after which they returned to control numbers. It was evident that up to 40% of the cells within the ventricular zone were destroyed following brief maternal heat

ISSN:0040-3709    

DOI:10.1002/tera.1420390209

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

年代:1989

数据来源: WILEY

摘要:

AbstractZinc deficiency (ZD) is teratogenic in rats, and fetal skeletal defects are prominent. This study identifies fetal skeletal malformations that affect calcified and non‐calcified bone tissue as a result of gestational zinc deficiency in rats, and it assesses the effect of maternal ZD in fetal bone calcification. Pregnant Sprague‐Dawley rats (180–250 g) were fed 1) a control diet (76.4 μg Zn/g diet) ad libitum (group C), 2) a zinc‐deficient diet (0 μg/g) ad libitum (group ZD), or 3) the control diet pari‐fed to the ZD rats (group PF). On day 21 of gestation, laparotomies were performed. Fetuses were weighed, examined for external malformations, and stained in toto with a double‐staining technique for the study of skeletal malformations. Maternal and fetal tissues were used for Zn, Mg, Ca, and P determinations. Gross external malformations were present in 97% of the ZD fetuses. No external malformations were found in fetuses from groups C and PF. Ninety‐one percent of cleared ZD fetuses had multiple skeletal malformations, whereas only 3% of the fetuses of group PF had skeletal defects; no skeletal malformations were found in fetuses from group C. Some of the skeletal malformations described in the ZD fetuses, mainly affecting non‐calcified bone, were not mentioned in previous reports, thus stressing the importance of using double‐staining techniques. Examination of stained fetuses and counting of ossification centers revealed important calcification defects in ZD fetuses. These effects were confirmed by lower Ca and P concentrations in fetal bone with alteratio

ISSN:0040-3709    

DOI:10.1002/tera.1420390210

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

年代:1989

数据来源: WILEY

摘要:

AbstractAbout 17% of embryos and fetuses in the SELH/Bc mouse stock have the anterior neural tube defect, excncephaly. No other malformations are seen. The genetic liability to exencephaly was shown to be probably genetically fixed in the SELH/Bc stock. This means that SELH/Bc embryos with successful neural tube closure are genetically the same as exencephalics. Females were significantly more likely to be affected than males (66% females).The pattern of morphological development events during anterior neural tube closure on days 8 and 9 of gestation was compared among 322 ICR/Bc (normal), 304 SWV/Bc (normal), and 265 SELH/Bc embryos. Anterior neural tube closure was found to follow a strikingly different pattern in almost all SELH/Bc embryos than in either of the normal strains or in previous published studies. SELH/Bc embryos lack the initial contact between the anterior folds in the posterior prosencephalon/anterior mesencephalon region (Closure 2). In spite of this, all but 17% manage to close the anterior neural tube by extending caudally the later occurring normal anterior zone of contact and fusion at the most rostral aspect of the prosencephalon (Closure 3) through the region of Closure 2 to meet the zone of closure of the rhombencephalon, Closure 4. Anterior neural tube closure was completed late, and in some SELH/Bc embryos, elevation and fusion in the mesencephalon did not occur at all.In histological sections of six‐ and eight‐somite embryos, elevated numbers of pyknotic cells in the neuroepithelium and mesenchyme, and elevated numbers of unstained inclusions in the neuroepithelium were found; but their relationship, if any, to the abnormal pattern of neural tube closure is not cl

ISSN:0040-3709    

DOI:10.1002/tera.1420390211

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

年代:1989

数据来源: WILEY