摘要:

AbstractThe purpose of this paper was to report the muscle variations in eleven cases of radial aplasia and to extract information relative to normal and abnormal limb muscle development. The cases all involved other defects ranging from acardia to “thrombocytopenia‐absent radius” (TAR) and included several multiple malformations. The muscle patterns did not seem to depend upon the etiology of the radial aplasia but appeared to be more dependent upon late embryonic or early fetal muscular repositi

ISSN:0040-3709    

DOI:10.1002/tera.1420270102

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

年代:1983

数据来源: WILEY

摘要:

AbstractPrenatal exposure to mirex, a chlorinated hydrocarbon insecticide, induces a high rate of perinatal death, but only a low incidence of visible abnormalities which could help to account for these deaths. This study is an attempt to determine the cause of these deaths. Pregnant rats were intubated with a moderate dose of mirex, in oil, 6 mg/kg/day, on days 8½‐15½ of gestation. Observations, on 78 control and 136 treated fetuses, were made on the morning before parturition was expected. Fetuses were sequentially exposed and electrocardiograms obtained with the fetus attached to the placenta and uterus. ECGs were evaluated for rate of beat, regularity of beat, PR intervals, and other features. Fetuses were examined for edema level and vitality. None of the controls were dead and none had abnormal ECGs. Of the treated group, 14% were dead, 16% had a first‐degree heart block, and 2% had a second‐degree heart block. Some (6%) had slow, feeble atrial beats only, possibly a third‐degree block, and appeared to be dying. The severity of the symptoms was proportional to the degree of visible edema. Most of the fetuses with little or no visible edema had normal ECGs, but the majority of the moderate to severely edematous fetuses (i.e., with a layer of subcutaneous edema across the back of 0.5 mm or more) had abnormal ECGs and/or were either dead or dying. These data show that the effects of mirex on the fetal cardiovascular system are a major factor in inducing prena

ISSN:0040-3709    

DOI:10.1002/tera.1420270103

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

年代:1983

数据来源: WILEY

摘要:

AbstractThe objective of this investigation was to study the teratogenic effects of triamcinolone acetonide (TAC) in the rat. Pregnant females were injected intramuscularly once each day for three consecutive days (days 9–11, 12–14, or 15–17 of gestation) either with vehicle alone or with 0.125, 0.25, or 0.5 mg/kg TAC. All animals were euthanized on day 20 of gestation, and the fetuses were fixed for razor blade sectioning and skeletal examination. No maternal lethality was elicited in any of the treatment groups. There were decreases in fetal viability in the two higher dose groups treated on days 12–14 and the group treated with 0.5 mg/kg on days 15–17. These same three treatment groups showed significant increases in the percentage of malformed fetuses. The most prevalent malformation was cleft palate, with both complete and partial clefts being detected. Umbilical hernias and undescended testes were also found to be significantlymore frequent in the high‐dose group treated on days 12–14. A reduced degree of ossification was found in all TAC‐treated groups, but no specific skeletal malformations were detected. Fetal weight was significantly reduced in all TAC‐treated groups. The results demonstrate that (1) TAC affects a variety of developmental processes resulting in resorption, cleft palate, umbilical hernias, undescended testes, reduced ossification, and fetal growth retardation, (2) these teratogenic effects are elicited at doses causing no maternal lethality, and (3) fetal growth retardation can be produced at doses below those required to produce malformations and during periods of gestation where no malformations are produced, supporting the use of this parameter as a sensitive indicator

ISSN:0040-3709    

DOI:10.1002/tera.1420270104

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

年代:1983

数据来源: WILEY

摘要:

Abstract2‐Acetylaminofluorene (AAF), a highly effective mutagen and carcinogen, was tested as a direct‐acting teratogen in an embryo culture system. Concentrations of up to 75 μg/ml (336 μM) of AAF produced no detectable malformations and only minimal decreases in viability and growth of rat embryos explanted on day 10 (11th day of gestation; the day after fertilization was designated as day 0). Inclusion of a microsomal monooxygenase system (prepared from rat liver) in the culture medium, however, resulted in marked changes in viability and growth. All explanted embryos exposed to concentrations of AAF above 60 μg/ml (269 μM) plus the microsomal monooxygenase system exhibited readily observable malformations as well as significant decreases in size and macromolecular content. Two metabolites, N‐hydroxy‐2‐acetylaminofluorene (N‐OH‐AAF) and N‐acetoxy‐2‐acetylaminofluorene (AAAF), each produced malformations in the absence of a monooxygenase system. At concentrations of 25 μg/ml (105 and 88 μM) approximately 50% of the embryos exposed to these metabolites were malformed. The predominant malformations associated with the metabolites were ventrolateral protrusions and hypoplasia of the prosencephalic region, whereas AAF plus the monooxygenase system produced an interruption of neural tube closure. This suggested the possibility that other metabolites may participate in the AAF‐induced malformation syndrome. The addition of the monooxygenase system to cultures containing N‐OH‐AAF or AAAF increased the frequency of malformations without increasing

ISSN:0040-3709    

DOI:10.1002/tera.1420270105

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

年代:1983

数据来源: WILEY

摘要:

AbstractTeratogenic effects of the anticonvulsant drugs valproic acid (VPA) and diphenylhydantion (DPH) on the development of mouse embryos during early organogenesis were studied using the whole embryo culture technique. Embryos with one to seven somites were exposed in vitro to 50–375 μg/ml VPA or 15–135 μg/ml DPH for up to 42 hours and compared to control embryos cultured in 80% rat serum without either drug. For both VPA‐ and DPH‐treated embryos, a dose‐dependent increase in the frequency of abnormal embryos and a decrease in viability were found. VPA and DPH produced a similar pattern of defects. Drug‐induced anomalies included open neural tubes in the cranial regions, abnormal body curvature, craniofacial deformities, and yolk sac defects. Ultrastructural changes were noted in the neuroepithelium of exencephalic VPA‐treated embryos. Growth and development were retarded in embryos exposed to>35 μg/ml DPH or>50 μg/ml VPA as indicated by the decrease in protein and DNA content and the reduction in somite number, crown‐rump length, and yolk sac diameter. On a molar basis DPH was potentially more teratogenic than VPA, which correlates with the higher lipid solubility of DPH. With VPA, susceptibility to the drug depended on the developmental stage; e.g., at 150 μg/ml VPA the frequency of malformations was 70% in embryos with one to four somites as compared to 35% in embryos with f

ISSN:0040-3709    

DOI:10.1002/tera.1420270106

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

年代:1983

数据来源: WILEY

摘要:

AbstractIonic conditions were varied during homogenization of adult livers and during incubation of hepatic cytosol with glucocorticoid, and the effects on the detection of differences between inbred strains of mice for receptor levels were studied. When homogenized directly in 0.01 M Tris or homogenized in distilled water and then buffered to either 0.05 M Tris or 0.01 M potassium phosphate, A/J glucocorticoid receptor levels were greater than those of B10.A. However, when homogenized directly in 0.05 M Tris or buffered to 0.05 M potassium phosphate after homogenization in distilled water, A/J and B10.A had similar receptor levels. When buffered to 0.01 M Tris after homogenization in distilled water, A/J receptor levels were greater than those of B10.A but not significantly so. In Tris buffers, glucocorticoid receptor levels were higher when livers were homogenized directly in buffer than when liver homogenates were buffered after homogenization. This concentration effect is apparently due to the more rapid decay of glucocorticoid receptor in the lower molarity buffer. A reducing agent, thioglycerol, did not appear to affect either the rate of decay of the receptors or the measured level of receptor for B10.A and A/J. C57BL/6J receptor levels were measured in Tris buffers and had a similar relationship to A/J as did B10.A.

ISSN:0040-3709    

DOI:10.1002/tera.1420270107

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

年代:1983

数据来源: WILEY

摘要:

AbstractSubcutaneous injection of pregnant mice on day 8 of gestation with 1,000 mg/kg or 200 mg/kg of an aqueous solution of the sodium salt of acetazolamide, divided into three equal treatments at 8‐hour intervals, in two series of experiments performed 8 months apart on separately purchased random bred CD‐1 animals, resulted in the occurrence of a novel variant of the frontal bones of the skull when animals exposed in utero were examined at 62 ± 2 days postnatal.In its greatest manifestation this variation consisted of a 2–3 mm posteriad extension of the dorsomedial portion of the posterior margin of both bones, although all degrees of asymmetry and variations in the extent of involvement of the posterior margin of the bones were seen. This frontal extension variant was seen in 30.9 ± 4.7% and 53.1 ± 5.0% of the 97 and 98 specimens in the highdose groups, and in 8.1 ± 2.7% and 14.6 ± 3.7% of the 99 and 89 low‐dose specimens in the two series. It was not seen in untreated groups, or to any significant extent in vehicle‐treated groups, or in a treatment regime involving exposure during days 9–11 of gestation. It was also not seen in 2,110 specimens from four other series of experiments reported in detail involving the teratogens, trypan blue (two series), 5‐bromodeoxyuridine, or 2,4,5‐T, or in approximately 1,000 specimens from comparable experiments with a variety of pesticides (Maneb, Captan, Trifluralin, Decamethrin) or Thalidomide.In contrast, a morphologically analogous variant, accessory parietal, in which a suture in the anterodorsal surface of the parietal bones running posteromedial and seemingly delimiting a separate bone, is seen in all series. Although it looks as though frontal extension could be an accessory parietal fused with the frontal bone, observation of the specimens does not strongly support that relationship. Even if that were the case, it happens only in day‐8 acetazolamide exposure.From the rather extensive series of observations performed, it would appear that frontal extension is a specific response to in utero exposure to acetazolamide during

ISSN:0040-3709    

DOI:10.1002/tera.1420270108

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

年代:1983

数据来源: WILEY

摘要:

AbstractFrom 1964 to 1976, a cohort study was performed in West Germany to study the possible influence of various factors on pregnancy and child development. Results of the evaluation of 13,643 pregnancies are given with respect to possible teratogenetic effects of antiemetic drugs and sex hormones administered in early pregnancy. There was no evidence of an increased risk of major malformations following the intake of certain antiemetic drugs and progesterone. Also, the use of a hormonal pregnancy test was not significantly associated with an increase of major malformations.

ISSN:0040-3709    

DOI:10.1002/tera.1420270109

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

年代:1983

数据来源: WILEY

摘要:

AbstractThe chick embryo is a convenient experimental system for embryologic and teratologic studies. However, windowing eggs during the first day of incubation, a procedure that is required to expose embryos in ovo, frequently results in dysmorphogenesis. The frequency and severity of the particular anomalies caused by windowing are greater the younger the embryo at the time this procedure is done. At all stages examined, dysraphic defects of the neural tube are the most common anomaly present following windowing. Defects of the neural tube are virtually eliminated if the air space introduced over the embryo by windowing is filled with albumen or saline, and the egg (with its window sealed with tape) rotated 180°, so that the embryo rests subjacent to an undisturbed area of the shell. Subblastodermic injection of saline, a vehicle often used for teratogenic agents, has no adverse effects when eggs are subsequently filled with albumen or saline and rotated. Furthermore, known teratogens (e.g., colchicine, hyaluronidase) injected subblastodermically after windowing are active in eggs that are then filled with albumen or saline and rotated. Finally, the addition of albumen or saline, followed by rotation, may be delayed up to 3 hours without reducing the restorative effects of these two procedures. Our modified procedures for the handling of windowed eggs significantly increase the value of young chick embryos for studies of early developmental events

ISSN:0040-3709    

DOI:10.1002/tera.1420270110

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

年代:1983

数据来源: WILEY

摘要:

AbstractWomen exposed prenatally to diethylstibestrol (DES) develop a variety of reproductive tract anomalies. Most of these anomalies have been replicated in strain CD‐1 mice after similar DES exposure. Recently, impaired reproductive performance in DES‐exposed women has been reported. To see whether the mouse model also replicates this defect, at study of reproduction was performed. Pregnant CD‐1 mice were injected with DES and their female offspring were raised to breeding age. The latter were then exposed continuously to untreated males for a maximum of 4 months. Among 74 mated mice, 34 became pregnant and 11 of these pregnancies ended in abortion or stillbirth. Other anomalies encountered were: two fetuses with compressed heads, one of which seemed blocked from delivery by a vaginal adenocarcinoma; two uterine tumors, one of which was a teratocarcinoma; two teratomas located in uterine lumina; and two uteri containing placentas without embryos. Since the frequency of successful pregnancies in the DES‐exposed mice was reduced below control levels to a degree similar to that reported for DES‐exposed women, the validity of the mouse model has been confirmed for this chara

ISSN:0040-3709    

DOI:10.1002/tera.1420270111

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

年代:1983

数据来源: WILEY