摘要:

AbstractThe morphogenesis of conjoined twins is incompletely understood. We therefore conducted a postmortem study of dicephalus dibrachii dipus conjoined twins. The twins were born without pertinent history or prenatal diagnosis at 38 weeks and lived for several hours. External genitalia were female and partly duplicated; a caudal appendage was present in the thoracolumbar region. The heart and liver were shared and exhibited major abnormalities in configuration. Four lungs, three kidneys and adrenal glands, and two spleens were identified; biliary and upper gastrointestinal tracts appeared as mirror images. From these findings, we postulate three major sets of consequences arising from the anatomical disposition of the twin notochords (“paleoaxes”). 1) The degree of convergence/divergence of craniocaudal paleoaxes is variable. Convergences are maximal in the upper thoracic and sacral regions, where duplication of organs is minimal because of interaction aplasia. 2) In the horizontal plane, paleoaxes are sufficiently divergent to produce a degree of twin expression posteriorly, whereas anteriorly they converge to form a single, anterior, midline “neoaxis.” Interposed between these zones of paleoaxial and neoaxial expression are areas of variable interaction aplasia. 3) The left twin was in situs solitus; the right twin was in situs inversus in a manner resembling poly

ISSN:0040-3709    

DOI:10.1002/tera.1420400402

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

年代:1989

数据来源: WILEY

摘要:

AbstractA murine embryo culture model was developed to study the potential contribution of enzymatic bioactivation to the teratogenicity of phenytoin. To assess the relative embryonic and maternal contributions to bioactivation, embryos were cultured respectively alone or in the presence of an exogenous source of cytochromes P‐450 (P‐450), which are thought to bioactivate phenytoin to a teratogenic reactive intermediate. Embryological development from gestational day 9 to day 10 was assessed, and bioactivation was quantified by the irreversible binding of radiolabeled phenytoin to embryonic protein. Embryos cultured with phenytoin and an exogenous P‐450 bioactivating system showed a significant decrease in the incidence of turning and closure of the anterior neuropore, yolk sac diameter, and protein content as well as growth retardation. In the absence of an exogenous P‐450 system, phenytoin did not decrease the incidence of turning or anterior neuropore closure but did cause growth retardation and a lesser but significant reduction in yolk sac diameter and embryonic protein content. An exogenous P‐450 system enhanced the bioactivation of phenytoin, although significant activity also was detectable in embryos cultured without an exogenous bioactivating system. These results suggest that the embryo itself can enzymatically bioactivate embryotoxically significant amounts of phenytoin, and that bioactivation and embryotoxicity can be further enhanced, qualitatively and quantitatively, by an exogenous P‐450 system, implicating a possible maternal contribution to phenytoin ter

ISSN:0040-3709    

DOI:10.1002/tera.1420400403

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

年代:1989

数据来源: WILEY

摘要:

AbstractActivation of the inducible heat shock 71 genes and their role in the heat shock response was studied in vitro in 9.5 day‐old rat embryos at neural tube closure. The transcriptional response of a 71 kilodalton (kD) heat shock gene induced after various regimes of heat shock and acquired thermotolerance was investigated. Expression and accumulation of the heat shock (hs) 71 mRNA in the neuroectoderm was studied by Northern and dot blot analysis. Specific expression in various cell types and regions of the neuroectoderm were examined by in situ hybridization.Exposure of embryos to a heat shock at 43°C for 7.5 min caused high levels of hs mRNA 71 accumulation in the neuroectoderm, pronounced protein synthesis inhibition, and regulated recovery. Specific neuroectoderm cell death followed, resulting in major developmental defects of the eye and forebrain region. A mild heat shock of 42°C for 10 min induced the heat shock response, hsp synthesis, and cell recovery, but produced no cell death or deformities. Preheating the embryo at 42°C resulted in acquired thermotolerance to an otherwise teratogenic 43°C heat shock. Thermotolerance was associated with a rapid recovery of protein synthesis associated with hs 71 mRNA expression. Dot blot analysis showed that after a 42°C heat shock, 71 mRNA was rapidly transcribed and transported into the cytoplasm where it was degraded within 2 hr of the initial response. The results suggest that the heat shock protein (hsp) 71 gene may have a protective rather than a rescuing fu

ISSN:0040-3709    

DOI:10.1002/tera.1420400404

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

年代:1989

数据来源: WILEY

摘要:

AbstractPregnant Sprague‐Dawley dams were exposed to a liquid ethanol diet (35% ethanol‐derived calories), an isocaloric pair‐feeding regimen, restraint stress, or no treatment during the last week of pregnancy. Dams in each group received injections of testosterone propionate (TP) or the oil vehicle from days 15 through 20 of gestation. Birthweights of pups from dams administered TP and also exposed to alcohol, pair‐feeding, or restraint stress were significantly depressed by as much as 40 percent compared to oil‐injected counterparts. Prenatal exposure to alcohol, pair‐feeding, or restraint stress in the absence of TP did not significantly depress birthweight, nor was birthweight depressed in animals from dams injected with TP but exposed to no other treatment. Results are discussed with respect to an inhibition of fetal growth produced by a possible synergism between activation of the hypothalmic‐pituitary‐adrenal axis and elevated

ISSN:0040-3709    

DOI:10.1002/tera.1420400405

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

年代:1989

数据来源: WILEY

摘要:

AbstractThe Moebius syndrome consists of congenital seventh nerve palsy associated with other cranial nerve palsies, most often of the sixth, and/or musculoskeletal abnormalities. A retrospective study of the events of pregnancy in 15 cases was undertaken, after a rat animal model showed that abdominal trauma, uterine vessel clamping and handling and hyperthermia caused bilateral brainstem lesions in fetal rats. Eight of the 15 cases surveyed included a possible associated event during pregnancy; hyperthermia, previous uterine surgery, electric shock, failed abortion, prolonged rupture of the membranes, or alcohol abuse. These events can be correlated with animal studies that involve acute uteroplacental vascular insufficiency produced by a variety of methods. The cause of most cases of Moebius syndrome is probably a transient ischemic/hypoxic insult to the fetus.

ISSN:0040-3709    

DOI:10.1002/tera.1420400406

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

年代:1989

数据来源: WILEY

摘要:

AbstractThe effects of nifedipine (40–100 μmol/kg), nitrendipine (40 and 80 μmol/kg), hydralazine (381 and 763 μmol/kg), felodipine (12 μmol/kg), and the pharmacologically inactive first‐step metabolite of felodipine, H152/37 (80 μmol/kg) were studied in rabbits (New Zeeland White) after oral administration on day 16 of gestation. The vasodilating drugs—nifedipine, nitrendipine, felodipine, and hydralazine—all induced digital defects in the fetuses. The defects consisted of a reduction, absence, or abnormal structure of the distal phalanx of especially the fourth digit on the hind paw(s). Histologically, a disturbed differentiation of the cartilage, and secondarily also of the ossification centre and joint structure of the distal phalanx, was observed. In contrast, no digital abnormalities were observed after administration of vehicle or H152/37. The findings that vasodilators with different structures, like dihydropyridines and hydralazine, induced the same type of digital defects strongly suggest that the observed phalangeal defects are secondary to pharmacological action, and not related to chemical structure. A decrease in uteroplacental blood flow, caused by excessive hypotension, is discussed as the most probable mechanism underlying the obse

ISSN:0040-3709    

DOI:10.1002/tera.1420400407

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

年代:1989

数据来源: WILEY

摘要:

AbstractWe investigated whether there is a difference in timing between the sexes of mouse embryos with regard to digit and palatal formation at midgestation by using a simple method of sex chromatin analysis for rodent embryos. At day 14.4 of gestation, although the mean body weight of male embryos was greater than that of female embryos, digit and palatal formation of female embryos was found to be more advanced than in males when compared according to their body weight. This was contrary to our previous finding of digit formation at the earlier stage (day 12.0 of gestation): namely, that digit development was more advanced in male embryos than in female embryos even when two sexes were compared according to their body weight. Thus, the development of female embryos catches up with that of male embryos at the later stages of midgestation. The period for digit development must be longer in male embryos than in female embryos. If mothers are exposed to some teratogens, a sex difference in incidence of digital defects might be produced.

ISSN:0040-3709    

DOI:10.1002/tera.1420400408

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

年代:1989

数据来源: WILEY

摘要:

AbstractFollowing exposure to bromodeoxyuridine (BUDR), acetazolamide (ACZM), trypan blue (TRBL), cortisone (CORT), or diphenylhydantoin (DPH), alizarin‐stained, cleared fetuses were examined at 18 days postcoitus for unossified cervical vertebral central; number of ossified caudal vertebrae; number of ribs; and ossification of sternebrae, metatarsals, metacarpals, and phalangeal rows. At all teratogenic doses, in no vehicle‐treated groups, and rarely in lower‐dose groups, there were significant increases in frequency of unossified cervical centra, the first vertera (C1) being most often affected, and C7 least often affected. In the high‐dose CORT group, there was a significant correlation between unossified C1 and cleft palate. No association between abnormality and reduced ossification of cervical vertebrae was seen in other series examined, nor was there any correlation between litter size and abnormality. With minor complications, the number of ossified caudal vertebrae was significantly reduced after exposure at teratogenic dose levels to all compounds except DPH. Although caudal and cervical ossification were correlated with each other in those series examined, neither was correlated with abnormality. Frequency of 14 ribs was increased in BUDR, ACZM, and TRBL but not CORT or DPH. Other parameters were essentially unaffected. Significantly increased frequency of abnormality, when contrasted with untreated or vehicle‐treated groups, was seen at high‐dose levels in all but DPH treatments, and mortality was increased in ACZM D9‐11, TRBL, and CORT. These studies show that reduced ossification of cervical centra is an excellent indicator of prenatal exposure to noxious substnces, and caudal vertebrae appear to be useful as well. Increased frequency of 14 ribs occurred for all strong teratogens utilized if they were administered on day 7 or day

ISSN:0040-3709    

DOI:10.1002/tera.1420400409

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

年代:1989

数据来源: WILEY

摘要:

AbstractA comparative analysis of the teratogenic effects of L‐asparaginase on 10.5‐day rat embryos after 24 and 48 hours of exposure in vitro, respectively, were performed. Several medium concentrations of L‐asparaginase (0.05, 0.25, and 1.5 IU/ml) were tested in both embryo series. Resulting embryos were submitted to morphological studies in a search for a specific route of pathogenesis. Morphological alterations of the visceral yolk sac were also studied to investigate its contribution to L‐asparaginase teratogenicity in rats. Main embryonic malformations (open truncal neural tube, open encephalic vesicles, anophthalmia, lack of inversion, abnormal frontolateral protrusions, great vascular dilations at the cephalic level) and developmental retardation were already generated after the first 24 hours of culture (embryos of 10.5 days) and presented a dose‐response related to an early mesenchyme deficiency. Reduced number of mesenchymal cells was more evident in embryos of 10.5 days than those of 11.5 days, suggesting the existence of a later compensatory mechanism of cellular proliferation in the older embryo. Visceral yolk‐sac endodermal cells at both embryonic stages were greatly deformed and enlarged by an incerase of the high electron‐dense vacuolar system. Therefore, both a blockage of the processes of lysosomal digestion and derived trophic deficiencies probably existed. A double teratogenic mechanism for L‐asparaginase is postulated: a direct action mainly in younger embryos (before invagination of the embryo into the yolk sac) and a yolk s

ISSN:0040-3709    

DOI:10.1002/tera.1420400410

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

年代:1989

数据来源: WILEY

摘要:

AbstractExposure of pregnant mice on gestation day (gd) 8 to 1 MHz continuous‐wave ultrasound (0, 0.05, 0.50, or 1.00 W/cm2) was reported previously to result in a slight (nonsignificant) increase in malformations. The present study was conducted in a similar fashion using pulsed ultrasound but was designed to maximize the likelihood of finding effects of gd 8 ultrasound exposure on prenatal development. Pregnant ICR mice (approximately 60 animals/group) were exposed on gd 8 to pulsed ultrasound with a center frequency of 1 MHz at levels of 0 (sham control), 0.05, 0.50, or 1.00 W/cm2(spatial average, temporal average intensities; ISATA) with a spatial peak, pulse average intensity (ISPPA) of 90 W/cm2and pulse duration of 6.5 μsec. Anesthetized animals were placed in a degassed water bath (30°C) and exposed for two 10 min intervals during which the beam was centered 1 cm on either side of the abdominal midline. On gd 17, dams were killed; the uterus and its contents were weighed and examined; and live fetuses were weighed and examined for external, visceral, and skeletal malformations. Although one female in the 0.50 W/cm2group and seven animals in the 1.00 W/cm2group died following exposure, no other significant change from controls was seen in any maternal or fetal parameter evaluated. Thus the results of this study indicate that there was no detectable effect on prenatal development of mice following exposure to ultrasound on gd 8 (a time of maximal sensitivity), even at exposure intensities that were lethal to some maternal anim

ISSN:0040-3709    

DOI:10.1002/tera.1420400411

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

年代:1989

数据来源: WILEY