摘要:

AbstractNitrofen (2,4‐dichloro‐4′ ‐nitrodiphenyl ether) is an herbicide with potent teratogenic activity in rodent species. The present study was an extension of previous efforts to characterize the distribution and metabolism of nitrofen in pregnant rats. Following a single p.o. exposure to radiolabeled compound on day 10 of pregnancy, maternal and embryonic tissues were collected at intervals from 1.5 to 72 hours. Radioactivity was accumulated and retained in maternal fat for over 72 hours. Peak levels were reached in other maternal organs at 3–12 hours. The half‐life in maternal plasma was estimated to be 42 hours. Radioactivity was first detected in the embryonic compartment at 3 hours and continued to increase through the 72‐hour time point. HPLC analysis indicated that the parent compound is initially deposited in maternal fat and after 48 hours redistributes to other maternal organs and to the embryo. The 5‐hydroxy derivative was the major nitrofen metabolite found in maternal tissues, while the 4′‐amino and 4′‐acetylamine derivatives were found at lower levels and all exhibited single‐phase kinetics. The parent compound alone was found in the embryo, and levels increased gradually as nitrofen redistributed from the fat at 48 hours after exposure. The results of this and other studies of nitrofen metabolism in pregnant rats suggest that its teratogenicity is not mediated via generation of mutagenic intermediates through nitroreduction of the parent compound. Rather, the embryo is exposed to the parent compound alone and appears to be a deep compartment for

ISSN:0040-3709    

DOI:10.1002/tera.1420340202

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

年代:1986

数据来源: WILEY

摘要:

AbstractIsotretinoin ingestion during the first trimester of human pregnancy can induce malformations of the skull, ears, face, central nervous system, eyes, palate, lungs, circulatory system, limbs, and digits. A single oral dose of isotretinoin on day 8 of gestation in hamsters induces a similar syndrome of congenital malformation. The present study concerned scanning electron microscopic (SEM) observation of embryonic and fetal hamster craniofacial structures at 4, 8, 12, 24, 48, and 72 hr after administration of an oral dose of 50 mg/kg isotretinoin or an equivalent volume of the vehicle. The variability in development among control embryos recovered 4 hr after treatment precluded objective assessment of pathologic change by SEM at very early time points. Craniofacial damage was obvious within 8–12 hr of isotretinoin treatment, and it included hypoplasia of the maxillary and mandibular processes of the first branchial arch, a rudimentary second arch, and apparent collapse of the forebrain. Equivalent fusion between the lateral nasal process and the maxillary process and between the medial nasal process and the maxillary process in treated and control embryos accounts for the very low incidence of cleft lip observed in fetuses. The terminal microstomia was not associated with excessive merging or overgrowth of the first arch components. Hypoplasia of the first arch can account for retinoid‐induced macrostomia and microsto

ISSN:0040-3709    

DOI:10.1002/tera.1420340203

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

年代:1986

数据来源: WILEY

摘要:

AbstractAcrolein, a three‐carbon unsaturated aldehyde, is teratogenic to rats in vivo following intraamniotic administration but has been reported not to be teratogenic in vitro in the rat whole embryo culture system. In this study the effects of acroleion on rat embryos cultured in the standard medium consisting of rat serum were assessed over a narrow‐concentration range. Additionally, a comparison was done of the effects of culture in a serum medium vs. a serum‐free medium. In the serum medium acrolein caused 100% embryolethality at 140 μM and was found to be teratogenic in the concentration range of 80–120 μM. In the serum‐free medium acrolein was 100% embryolethal at 20 μM and was teratogenic in the range of 5–15 μM. The EC50for malformations in the serum medium was 137 μM, whereas that for embryolethality was 115 μM; the EC50s for malformations and embryolethality in the serum‐free medium were 2.8 μM and 8.3 μM, respectively. Malformations were observed in the brain, facial area, and heart in addition to blebs and twisted or kinked bodies. Decreases in yolk sac diameter, crown–rump length, head length, number of somites, morphological score, and protein content were observed within the teratogenic ranges in each type of medium. Thus acrolein is teratogenic and embryolethal in vitro as well as in vivo. Dissociation between embryolethality and teratogenicity was seen in the serum‐free medium. The slope of the acrolein log concentration‐response curve in the serum‐free medium was twice that in the serum medium, indicating that acrolein may have a different mecha

ISSN:0040-3709    

DOI:10.1002/tera.1420340204

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

年代:1986

数据来源: WILEY

摘要:

AbstractIn several studies investigators have suggested that maternal use of exogenous sex hormones during early pregnancy may be associated with various congenital malformations. A group of malformations, the VACTERL (vertebral, anal, cardiac, trachea, esophageal, renal, limb—acronym) association, has been statistically associated with maternal exposure to exogenous sex hormones during the first trimester of pregnancy. The VACTERL association is a nonrandom group of major malformations that occur together more often than would be expected on the basis of chance. To assess this association, we conducted a case‐control study of first‐trimester exposure to sex hormones among mothers of 34 infants with the VACTERL association and of 1,024 comparison infants with one or more of ten major malformations or Down syndrome. The study subjects were malformed infants born between July 1970 and June 1979 and registered in a population‐based birth defects registry. Information concerning the use of exogenous sex hormones during pregnancy was obtained by systematically interviewing the mothers of the malformed infants. Most of the mothers were interviewed within 6 months of their children's births. Each mother was interviewed within a year of her child's birth. We found an odds ratio of 0.98 (90% confidence limits 0.40, 2.38) for the relationship between VACTERL association and use of any sex hormone in the first trimester of pregnancy. Our study had adequate statistical power to detect a true relative risk of 2.8 or

ISSN:0040-3709    

DOI:10.1002/tera.1420340205

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

年代:1986

数据来源: WILEY

摘要:

AbstractAlthough neural tube defects are a common congenital anomaly, their etiology is not known. Human studies have emphasized the pathology and epidemiology of the defects and suggest that in the majority of cases the etiology is multifactorial. Factors which appear possibly to be important are genetic predisposition, maternal illness, and fetal drug exposure. Animal studies have utilized naturally occurring neural tube defects and teratologically induced lesions. No animal model has been convincingly established as the equivalent of human neural tube defects. However, animal models have allowed investigation of the mechanisms of suggested human teratogens and determination of the pathogenesis of naturally occurring animal defects. Their most important contribution has been in furthering the understanding of the normal mechanisms of neural tube closure. It may be through this understanding that the etiology of human neural tube defects will be determined.

ISSN:0040-3709    

DOI:10.1002/tera.1420340206

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

年代:1986

数据来源: WILEY

摘要:

AbstractHamster dams dosed continously with arsenate and exposed to short‐term hyperthermia produced a greater percentage of malformed offspring than did hamster dams dosed with arsenate alone. Hamsters receiving both treatments possessed elevated arsenic concentrations in the maternal blood and placentas immediately after cessation of the hyperthermic insult. Blood levels of arsenic were the same as those of animals not receiving the heat treatment within several hours post‐hyperthermia; however, arsenic concentrations remained elevated in placentas, the duration being dependent on the dose of arsenate. We suggest that the rise in placental arsenic concentrations is the basis of the increase in the production of fetal malformations for hamsters treated continuously with arsenate and heat stressed during critical organogene

ISSN:0040-3709    

DOI:10.1002/tera.1420340207

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

年代:1986

数据来源: WILEY

摘要:

AbstractAcetazolamide, a carbonic anhydrase inhibitor, induced right forelimb ectrodactyly in rat fetuses when the mothers were treated on late day 10 and early day 11 of gestation. Coadministration of the selective alpha‐1‐adrenergic agonist phenylephrine significantly increased the incidence of acetazolamide‐induced right forelimb ectrodactyly while failing to induce the lesion when administered alone. Pretreatement with the alpha‐adrenergic antagonists phenoxybenzamine and prazosin prevented the phenylephrine‐induced increase in right forelimb ectrodactyly. In addition, treatment with either phenoxybenzamine or prazosin in the absence of stimulation with phenylephrine significantly decreased the incidence of acetazolamide‐induced ectrodactyly. The results suggest an adrenergic component in acetazolamide teratogenesis. Alterations in uterine blood flow are discussed as a plausible mechanism for the modification of the incidence of ectrodactyly by these adrene

ISSN:0040-3709    

DOI:10.1002/tera.1420340208

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

年代:1986

数据来源: WILEY

摘要:

AbstractIn the rabbit, ovulation and conception occur during an 8–10 hour period immediately following mating (“reflex ovulation”). We report here that live Newcastle disease virus (NDV; an avian paramyxovirus) injected into rabbits immediately following mating resulted in a high frequency of embryo death at a wide range of developmental stages. When measured at midterm, a greater than threefold increase in embryo mortality was observed (24.7% vs. 6.8%). Aneuploidy of a small acrocentric chromosome was observed in three of 60 live midterm embryos recovered from NDV‐injected does. No aneuploidy was observed in 52 live midterm embryos from control, saline‐injected does. These observations suggest that the NDV‐exposed rabbit can provide a useful model for the study of the teratological effect of virus exposure occurring at or about the time of meiosis, ovulation, and

ISSN:0040-3709    

DOI:10.1002/tera.1420340209

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

年代:1986

数据来源: WILEY

摘要:

AbstractEmbryos from mice exposed to lead chloride (20 μg/gm body weight) by a single intravenous injection on day 8 of gestation were examined regarding the number and distribution of their primordial germ cells on 4 consecutive days of development. The cells, visulized by histochemical staining for alkaline phosphatase, showed a normal body distribution but were significantly fewer at all four stages compared with those of control embryos of corresponding age. Furthermore, the staining of the primordial germ cells was much weaker in the embryos from the lead‐treated dams than in those from control dams, suggesting that the lead had interfered with the production or activity of alkaline phosphatease. It is assumed that these effects could have contributed to the fertility reduction previously observed in female offspring of mice exposed to lead at an early stage of pregnan

ISSN:0040-3709    

DOI:10.1002/tera.1420340210

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

年代:1986

数据来源: WILEY

摘要:

AbstractAdministration of nitrofen (2,4‐dichloro‐4′‐nitrodiphenyl ether) during organogenesis in rodents produces neonatal lethality accompanied by lung hypoplasia, diaphragmatic hernias, heart anomalies, and hydronephrosis. Different strains of rats, Long Evans Hooded (LEH) and Sprague‐Dawley (SD), are reported to have different malformation responses to prenatal exposure, which could be due to true strain differences, to different levels and times of exposure, or to the use of different methods for detecting visceral malformations. In the present study, LEH, SD, and „virus‐antibody‐negative”︁ SD (VAN‐SD) rats were identically exposed to 0, 6.25, 12.5, or 25 mg/kg/day of nitrofen by gavage in corn oil on days 6–15 of gestation. At term, half of the litter was examined by the Wilson method of razorblade sectioning and the remainder by a modified Staples method of fresh visceral examination. The two methods were equally sensitive for detecting diaphragm, kidney, and lung anomalies, whereas heart malformations were more frequently identified with fresh visceral examination. The frequency of total malformations did not vary across strains at any dose, but there were substantial differences in the pattern of malformations in each strain. SD and VAN‐SD rats responded similarly for all malformations, but had significantly higher incidences of diaphragm and lung anomalies than LEH rats. Conversely, LEH rats had significantly elevated levels of kidney anomalies compared to SD and VAN‐SD rats, whereas frequency of heart malformations was low and comparable across strains. These results suggest that true strain differences exist in the pattern of malformation produced by prenatal exposure to nitrofen that may be based on genetic differences

ISSN:0040-3709    

DOI:10.1002/tera.1420340211

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

年代:1986

数据来源: WILEY