摘要:

AbstractTo study the effect of Cyclophosphamide (CPA) treatment of pregnant mice during the preimplantation period on different embryonic cells even before implantation, the cell numbers of the immunosurgically isolated inner cell mass (ICM) and the blastocyst total cell number (BTCN) were determined in late blastocysts. In animals treated at 2 P.M. on day 2 of pregnancy a dose‐related reduction of the cell numbers was found for both ICM and BTCN in morphologically normal late blastocysts (day 4, 8 A.M.) at CPA doses of 20–60 mg/kg which did not induce embryonic death before implantation but did later during organogenesis. At identical CPA doses the reduction of the cell numbers of the ICM was significantly greater than that of the BTCN. These data provide evidence for a differential sensitivity of the two groups of cells in preimplantation mouse embryos (trophectoderm and ICM) to maternal CPA treatment even before implantat

ISSN:0040-3709    

DOI:10.1002/tera.1420230103

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

年代:1981

数据来源: WILEY

摘要:

AbstractPreimplantation mouse embryos were cultured for 48 hours from the four‐cell and eight‐cell stage to the blastocyst stage in the presence of Cyclophosphamide (CPA) or one of its metabolites–4‐hydroperoxy‐CPA (4‐HP‐CPA), phosphoramide mustard (PAM), and acrolein (Acr)‐to identify the metabolite which is embryotoxic after CPA treatment of pregnant mice during the preimplantation period. The dose‐response relations for the inhibition of blas‐tulation revealed identical inhibition curves for PAM and 4‐HP‐CPA (in solution 4‐HP‐CPA immediately decomposes to 4‐hydroxy‐CPA (4‐OH‐CPA)). These two metabolites are inhibiting blastulation in vitro at concentrations that are 10,000 times lower than CPA and 100 times lower than acrolein. When blastocysts which had developed in the presence of CPA and its metabolites in vitro were subsequently cultured in inhibitor‐free medium NCTC‐109, the same dose‐response relationship pattern was obtained. Since 4‐OH‐CPA decomposes into acrolein and PAM in vivo and in vitro and since PAM and 4‐OH‐CPA exhibit identical embryotoxicity towards preimplantation embryos in vitro, PAM probably also is an active embryotoxic CPA metabolite in vivo before implantation. This result is discussed in relation to the importance of alkylating CPA metab‐olites in cancer treatmen

ISSN:0040-3709    

DOI:10.1002/tera.1420230104

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

年代:1981

数据来源: WILEY

摘要:

AbstractThe effects of glucocorticoids on fetal growth and development in the rat were investigated. Pregnant rats were injected subcutaneously on gestational days 12 and 13 with betamethasone (0.18 or 0.42 mg), with dexamethasone (0.12 or 0.24 mg), or with physiological saline. Fetuses at day 21 of gestation were weighed, cleared, and stained for calcification with Alizarin Red S. Fetal weight was significantly reduced at both dose levels of each steroid; a greater reduction occurred with the higher dose. Retardation of growth and of calcification of bones in the axial skeleton occurred at both doses; there was greater retardation with the high dose. In the appendicular skeleton there was enhanced calcification of some bones with the low dose, and a retardation of calcification with the high dose of each steroid.The present findings show that different regions of the fetal skeleton may respond discordantly to the effect of glucocorticoids depending on the dose.

ISSN:0040-3709    

DOI:10.1002/tera.1420230105

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

年代:1981

数据来源: WILEY

摘要:

AbstractThe susceptible stages and the malformation pattern produced by excess retinoic acid were investigated in rat fetuses. Retinoic acid (120 mg/kg body weight, suspended in rape oil) was administered orally to pregnant females on one of the first 20 days of gestation. Fetuses were examined for external and, after visualization of the skeleton with alizarin red, for skeletal malformations on the 21st day of gestation. Retinoic acid was highly embryolethal when administered on days 9 and 10 of gestation (96.2 and 100% resorptions). The earliest teratogenic effect of retinoic acid was noted on the 9th day of gestation. Severe multiple defects were produced by retinoic acid administration on days 9 and 11 of gestation, but more specific malformations involving the axial skeleton, the fore‐ and hindlimbs, and cleft palate resulted from treatment on days 12–18 of gestation.Cycloheximide, an inhibitor of protein synthesis, reduced the incidence of limb defects induced by retinoic acid. This result indicates that the teratogenic effect of retinoic acid on limb morphogenesis may be dependent upon continuous protein synthesis and is compatible with the view that vitamin A may act like a horm

ISSN:0040-3709    

DOI:10.1002/tera.1420230106

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

年代:1981

数据来源: WILEY

摘要:

AbstractA group of 88 spontaneously occurring variations of the skeleton were studied in adult CD‐1 mice which had been exposed in utero to the herbicides 2,4,5‐T or Trifluralin, administered to their dams by gavage, in an attempt to detect subtle biological effects of these compounds even in the absence of gross malformations. Sixty‐seven characters showed variation in this population. Of these, 19 were significantly different in frequency from untreated controls in mice having received a teratogenic dose of 2,4,5‐T, with an average difference of 23.7%. Seventeen of them were increased in frequency. By contrast, only three traits differed from untreated among mice receiving a no‐effect dose of 2,4,5‐T. Twelve traits differed significantly from untreated in the Trifluralin‐treated group; the average difference was 18.8%, with 10 of the traits being increased in frequency.Two clusters of affected variants specific to the 2,4,5‐T high dose group included frontal bone variants in the skull (presence of an interfrontal bone and fusion of the frontals) and variants in the cervical vertebrae (imperfect foramina in the first and second cervicals, dyssymphysis of the second cervical, and a shift of the arch foramen from the fourth to the fifth cervical). Two other effects peculiar to the 2,4,5‐T‐treated specimens were a loss of the prominent dorsal spine of the second thoracic vertebra and a reduction in the number of caudal vertebrae. The most obvious effects specific to the Trifluralin treatment were an increase in occurence of 14 ribs, an undoubled foramen ovale, and the occurence of accessory foramina in the cervical vertebrae. A striking increase in frequency of parted frontals was seen in both 2,4,5‐T high dose and Trifluralin‐treated groups.The skeletal variant assay system may be useful as a postnatal screen for detecting prenatal exposure to potenti

ISSN:0040-3709    

DOI:10.1002/tera.1420230107

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

年代:1981

数据来源: WILEY

摘要:

AbstractSeveral compounds were administered to pregnant Wistar‐de‐rived rats either 24 or four hours prior to the recovery of day 10 embryos for in vitro culture in Waymouth's medium and fetal calf serum. The compounds tested were 2‐amino‐l,3,4,‐thiadiazole (thiadiazole), cadmium sulfate, l,2‐dibromo‐2,2‐dichloroethyl dimethyl phosphate (dibrom), 2‐(sec‐Butyl)‐4,6‐dinitrophenol (di‐noseb), lead nitrate, polybrominated biphenyls (PBB), sodium arsenate, and trypan blue. After 24 hours in culture, two thirds of the embryos were recovered for examination. The remaining one third were continued in culture until 42 hours. Recovered embryos were examined for rotation of the embryonic axis, heart rate, establishment of the visceral yolk sac circulation, somite number, growth of the limb buds, closure of the neural tube, and development of the allantois and amnion. All tested compounds inhibited the rat

ISSN:0040-3709    

DOI:10.1002/tera.1420230108

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

年代:1981

数据来源: WILEY

摘要:

AbstractA girl had persistent regurgitation of food from the first week of life until death at 19 weeks of age. Postmortem examination revealed widespread congenital anomalies including neuronal and neuroglial heterotopias of the thalamus and centrum semiovale on the left side, subependymal regions of both lateral and third ventricles, and both rostral medullary pyramids; and hy‐poplasia of the thalamus and cerebrum on the left side, and both lenticular nuclei. Moreover, the left lateral ventricle was moderately dilated, secondary to partial occlusion of the ipsilateral interventricular foramen. The left thalamus and hem‐icerebrum, as well as both lenticular nuclei, were remarkably small. The brain‐stem was normal except for pyramidal neuronal and neuroglial heterotopias, a finding not previously reported. The mechanism producing a small left thalamus, lenticular nuclei, and cerebrum on the left side is suggested as a combination of hypoplasia from aberrant migration of neuroepithelial derivations, a dilated left lateral ventricle, and degeneration of connecting nerve fibers. Decrease in size of the right lenticular nucleus is the result of hypoplasia alone. It is proposed that the lesions in the thalamus and cerebrum on the left side were responsible for regurgitation because of imbalanced supranuclear control of intact nuclei in the brai

ISSN:0040-3709    

DOI:10.1002/tera.1420230109

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

年代:1981

数据来源: WILEY

摘要:

AbstractMaternal administration of cadmium (Cd) has previously been shown to cause reduced lung weight and altered pulmonary surfactant accumulation in fetal rats. This leads to neonatal respiratory distress. In the present study the effects of Cd on the ultrastructural development of alveolar epithelium was studied to detect any alterations which could contribute to neonatal respiratory difficulties. Pregnant rats received 8.0 mg/kg body weight of CdCl2sub‐cutaneously on days 12–15 of gestation. Fetal tissue was examined by electron microscopy throughout the period of alveolar cytodifferentiation. The undiffer‐entiated epithelium of both treated and control fetuses was composed of simple columnar cells with apical and basal glycogen deposits. Cytodifferentiation in controls consisted of a gradual flattening of alveolar type I cells and the appearance of surfactant‐containing lamellar bodies in alveolar type II cells. Cytoplas‐mic glycogen was prominent up to day 20, then diminished to low levels on day 21. Epithelial differentiation in treated fetuses was delayed in most alveoli. On the two days before term some alveoli appeared normal, but many were retarded or arrested in their development. Cellular glycogen pools were reduced in treated alveoli and were absent just prior to birth. Lamellar bodies in treated alveoli were less numerous, correlating with the diminished pulmonary surfactant lecithin content reported earlier. These alterations in prenatal ultrastructural maturation could contribute to the postnatal respiratory difficulties previously

ISSN:0040-3709    

DOI:10.1002/tera.1420230110

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

年代:1981

数据来源: WILEY

摘要:

AbstractTwo infants with a striking pattern of associated malformations including agnathia, situs inversus, renal agenesis and ectopia, and multiple vertebral and rib abnormalities are described. It appears that these two infants represent a previously unrecognized malformation association that involves far more than developmental arrest of the mandibular arch. It is conceivable that a single defect at a very early stage in development could account for the multiple manifestations seen.

ISSN:0040-3709    

DOI:10.1002/tera.1420230111

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

年代:1981

数据来源: WILEY

摘要:

AbstractThe effect of L‐glutamic acid on the embryolethal and terato‐genic action of trypan blue was investigated in Wistar albino rats. L‐glutamic acid was either incorporated into the diet, from gestation day 2 to day 20, or suspended in sesame oil and administered by gavage, from gestation day 6 to day 10. The day of finding sperm in the vaginal smear was designated day 0 of pregnancy. A teratogenic dose of trypan blue was injected at day 8 of pregnancy, either intraperitoneally (14 mg/kg maternal body weight) or subcutaneously (160 mg/kg). The amount of glutamic acid consumed, after the injection of trypan blue, ranged from 600 to 1,500 mg/rat/day. Pregnancy was terminated at day 20, and the fetuses were recovered and examined. Glutamic acid failed consistently to protect the rat embryo against the lethal and teratogenic action of trypan blue. These results are in contrast to those obtained in mice. The administration of sesame oil alone was found to cause embryonic death, but not malforma

ISSN:0040-3709    

DOI:10.1002/tera.1420230112

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

年代:1981

数据来源: WILEY