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1. |
Effects of cadmium on reproduction, an epizootologic study |
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Teratology,
Volume 48,
Issue 3,
1993,
Page 189-196
I. A. Kreis,
M. de Does,
J. A. Hoekstra,
C. de Lezenne Coulander,
P. W. J. Peters,
G. H. Wentink,
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摘要:
AbstractThe Dutch part of Kempenland has been exposed to cadmium pollution since the last century. Experimental data suggest effects by cadmium on reproduction such as diminished fertility, decreased foetal growth, and specific malformations. Use was made of a historical cohort of dairy cows, ascertained from a surveillance program conducted by the regional Veterinary Health Service between 1976 and 1986. Ten dairy farms in the cadmium region were matched by size with 40 dairy farms from a reference area. Logistic models were used to calculate Odds (OR) and Rate Ratios (RR) and their 95% confidence interval. In total 4,039 exposed and 15,552 reference gestations were compared. The reasons for the slaughter of 574 exposed and of 2,824 reference cows were ascertained. A lower twinning rate [OR = 0.63 (0.47–0.84)] was found and more birth complications, for both calves [OR = 1.50 (1.25–1.80)]and cows [OR = 1.49 (1.24–1.79)]. More inseminations [OR = 1.20 (1.01–1.43)]were needed for conception in the exposed area. Deaths among twins [OR = 1.66 (0.90–3.07)] were not significantly higher. Perinatal death, premature death, age at, or reasons for, slaughter were not consistently different. These results are consistent with those of other observational and experimental studies. Extrapolation from these large domestic animals to humans is problematic, as is the more frequent extrapolation from rodents to humans. It can be concluded that longterm exposure to low levels of cadmium is associated with impaired reproduction in dairy COWS. © 1993 Wiley
ISSN:0040-3709
DOI:10.1002/tera.1420480302
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1993
数据来源: WILEY
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2. |
Retinoic acid induces changes in the rhombencephalic neural crest cells migration and extracellular matrix composition in chick embryos |
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Teratology,
Volume 48,
Issue 3,
1993,
Page 197-206
J. A. Moro Balbás,
A. Gato,
M. I. Alonso Revuelta,
J. F. Pastor,
J. J. Represa,
E. Barbosa,
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摘要:
AbstractChick embryos at 9–10 stages (Hamburger and Hamilton: J Morphol 88:49–82, 1951) have been treated with all‐trans retinoid acid (RA) (0.5 μg, 1.5 μg, and 2.5 μg) to determine the pattern and mechanism of RA‐induced effects on early cephalic development. We found that while 0.5 μg RA did not produce any significant dysmorphogenesis, 2.5 μg RA elicited wide malformation of both cephalic and trunk regions. However, 1.5 μg RA produced selective and specific changes at the cephalic level, which consisted of morphological alterations, changes in neural crest cells (NCC) migration and extracellular matrix (ECM) composition. Morphological alterations included hypoplasia of the first three branchial arches, swelling of either anterior cardinal veins or dorsal aortae, and atrophy of branchial arch arteries. Concurrently NCC did not migrate away, remaining clustered on the dorsal surface of the rhombencephalon, and in some cases they shifted into the neural tube cavity. Accordingly, the second branchial arch showed a reduction of the mesenchymal cellular population. The extracellular matrix in RA‐injected embryos showed changes in glycosaminoglycans (GAGs) concentration as compared with controls, that is, an increase in the non‐sulphated GAGs, stained with alcian blue 8GX at 2.5 pH, and a decrease in the sulphated GAGs stained with alcian blue 8GX at 1 pH. These quantitative changes reflected alterations in the pattern of distribution and composition of the GAGs within the cephalic ECM, which specifically consisted in an increase of the hyaluronic acid and a decrease of the chondroitin sulphate. Our findings indicate that RA is involved in abnormal cephalic development, suggesting that RA may effect neural crest cell migration via changes in the GAGs of the ECM. © 19
ISSN:0040-3709
DOI:10.1002/tera.1420480303
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1993
数据来源: WILEY
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3. |
Teratogenesis associated with oxydemeton‐methyl in the stage 12 chick embryo |
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Teratology,
Volume 48,
Issue 3,
1993,
Page 207-211
Daniel R. Lenselink,
John E. Midtling,
Gary L. Kolesari,
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摘要:
AbstractThe teratogenic potential of oxydemeton‐methyl (ODM) was investigated using a stage specific localized topical method of application to the stage 12 chick embryo. A dose of 0.01, 0.05, 0.10, 0.50, 1.0, or 2.0 mg/embryo was applied to the vitelline membrane directly above the stage 12 embryo. The embryo was then returned to the incubator and monitored daily until stage 41 (15 day). At stage 41 the embryo was autopsied and examined for gross external and internal malformations, wet weight, and crown‐rump length. Experimental data was compared to unopened and saline treated controls. At doses less than 0.50 mg/embryo, survival rates were high (>80%) but when that dose was exceeded, the survival rate fell significantly (P<0.001). A dose‐dependent increase in malformation rate was seen in all treatment groups with 0.10 mg/embryo, producing a maximum malformation rate (19/33) with minimum mortality (3/36). Crown‐rump lengths and wet weights were significantly less than controls in all treatment groups (P<0.001). Anomalies were primarily seen in the musculoskeletal (ventral midline, limb, and neck) and cardiovascular (ventricular septum and aortic arches) systems. Thoracogastroschisis and ventricular septal defects were the most common combination of malformations. Our data suggest that ODM is teratogenic when topically applied to the stage 12 chick embryo. © 1993 Wiley
ISSN:0040-3709
DOI:10.1002/tera.1420480304
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1993
数据来源: WILEY
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4. |
Chloroquine embryotoxicity in the postimplantation rat conceptus in vitro |
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Teratology,
Volume 48,
Issue 3,
1993,
Page 213-226
Jeffrey L. Ambroso,
Craig Harris,
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摘要:
AbstractThe embryotoxicity of the antimalarial drug chloroquine (CQ) was evaluated in vitro using the rat whole embryo culture system. CQ was found to be embryotoxic and dysmorphogenic when added directly to the culture media containing gestational day (GD) 10 rat conceptuses. Twenty‐six‐hr exposure to CQ elicited dose‐related decreases in embryonic crown‐rump length, protein and DNA contents and increases in the incidence of morphologically abnormal embryos. At 30 μM CQ, embryonic protein content was decreased to 67% and DNA content to 58% of control while the incidence of morphological abnormalities rose to 100%. Abnormal axial rotation, microophthalmia, and selective cephalic hypoplasia were the most common developmental abnormalities observed. Visceral yolk sac (VYS) vasculature and blood pigmentation were also decreased in a dose‐dependent manner, as was VYS DNA content (80% of control at 30 μM). VYS protein content, however, showed an alternate pattern of response, decreasing to 87% of control at 10 μM CQ but increasing to 125% of control at 30 μM. Histologic evaluation revealed that the cytoplasm of the VYS endoderm epithelium was distended due to vacuolization produced by CQ exposure. In the embryo proper, CQ inhibited cranial neural tube development and altered the morphology of cranial neural crest cells. These observations document the in vitro embryotoxicity of CQ and suggest altered VYS histiotrophic nutrition as well as direct embryonic effects as possible mechanisms of CQ embryotoxicity. © 1993 W
ISSN:0040-3709
DOI:10.1002/tera.1420480305
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1993
数据来源: WILEY
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5. |
Reporting of malformations in routine health registers |
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Teratology,
Volume 48,
Issue 3,
1993,
Page 227-231
Elina Hemminki,
Jouni Meriläinen,
Juha Teperi,
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摘要:
AbstractThe utility of three national registers—the malformation, birth, and hospital in‐patient discharge registers—in identification of malformations among 60,255 children born in 1987 in Finland was compared. Information in the malformation register is collected by specific reporting of physicians; information on the malformed children in the other two registers in 1987, through 1990 was routinely collected and identified by ICD 9‐codes (740‐759, 7886A). From October 1990 on, the ICD‐9 codes were omitted from the birth register and malformation data were asked only in a yes‐no question. In 1987, the malformation register included 1,032, the birth register 3,084 and the inpatient register 2,003 malformed infants identified up to the age of 1 year. There was underrepresentation of almost all malformation diagnoses in the malformation register. Individual linkage of the three registers showed that the malformation register revealed very few cases not recorded in the birth and the in‐patient registers. With the adoption of the new recording method in the birth register beginning in October 1990, reports of malformation declined by 75%. Our analyses showed that data sources based on diagnoses collected routinely and not requiring an explicit decision on whether or not a problem is a malformation, can be more useful for routine surveillance of occurrence of malformations. © 1993
ISSN:0040-3709
DOI:10.1002/tera.1420480306
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1993
数据来源: WILEY
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6. |
Evaluation of the effectiveness of a teratogen information service: A survey of patient and professional satisfaction |
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Teratology,
Volume 48,
Issue 3,
1993,
Page 233-245
C. J. Ludowese,
T. Marini,
R. Laxova,
R. M. Pauli,
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摘要:
AbstractWe have evaluated the effectiveness of the Wisconsin Teratogen Project (WTP), a teratogen information service, using two retrospective surveys. We surveyed medical professionals who utilized the WTP and patients who had received teratogen counseling in a clinic setting. The results from the medical professional survey indicated that medical professionals rely on the WTP for accurate and convenient teratogen information. A tendency to rely on the Physician's Desk Reference as an alternative resource was noted, reinforcing the need to encourage professionals to use teratogen information service projects. Major findings and conclusions from the patient survey included: patients found counseling to be most helpful if, whenever possible, numeric risks were provided; recommendations made in the absence of known risk were not considered by patients to be helpful for providing reassurance; overall compliance with recommendations was high but behavioral recommendations seemed to reduce reassurance and increase dissatisfaction with the service for some patients; and pregnant women exposed to low‐dose ionizing radiation were more likely to have considered termination of pregnancy prior to referral but were not more likely to terminate following counseling.Our findings suggest that although the WTP is considered an effective service overall, teratogen counselors should give special consideration to patient and counseling characteristics as these can significantly influence the perception of the risk counseling provided. Particular attention should be given to patients with low‐dose ionizing radiation exposure, since misperception of its teratogenic risk is extremely common. © 1993 Wiley‐Lis
ISSN:0040-3709
DOI:10.1002/tera.1420480307
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1993
数据来源: WILEY
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7. |
Fetal development in the rat following disruption of maternal renal function during pregnancy |
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Teratology,
Volume 48,
Issue 3,
1993,
Page 247-258
Robert J. Kavlock,
Tina Logsdon,
Jacqueline A. Gray,
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摘要:
AbstractPregnant Sprague‐Dawley rats received subcutaneous injections of mercuric chloride (1–4 mg/kg) on either gestation day 7, 9, 11, or 13 to determine effects of altered maternal renal function on embryonic and fetal development. Maternal renal function, assessed by urinanalysis, was markedly disrupted for at least 48 hours after treatment and resulted in decreased maternal body weight gain. Residual effects on maternal kidney weight were evident on GD 21 when the females were killed and the fetuses removed and examined for visceral and skeletal development. We did not observe an increased incidence of malformations in the offspring for exposure on any day of gestation. Maternal exposure to mercuric chloride slightly impaired fetal growth over several gestational exposures periods and changed the pattern of rib formation when exposure occurred early in organogenesis. The extent of the changes could not, however, be related to the immediate degree or duration of altered maternal renal function. Rather, we found correlations between lasting effects of exposure as measured by maternal renal weight on GD 21 and supernumerary lumbar rib induction on GD 7 and 9; while for the relationship with fetal weight, the strongest correlation with maternal kidney weight occurred following exposure on GD 9 (p<0.01), with weaker correlations (p<0.10) for GD 7 and 13 exposures. Maternal serum urea was negatively correlated with fetal weight from the GD 7 exposure. This study supports the concept that some specific forms of maternal toxicity may be associated with limited manifestations of developmental toxicity, but, in general, embryonic development was observed to proceed normally in the presence of marked disruptions in maternal renal physiology. Maternal toxicity, especially as routinely measured in developmental toxicity studies, cannot be looked upon as a single disease. Instead, each manifestation must be examined for what it signifies to the physiology and well being of the female and for cause‐and‐effect relationships with fetal observations. Maternal toxicity and developmental toxicity should not be etiologically linked solely because of their concurrent appearance on the dose‐response curve. © 1993 Wiley‐Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United State
ISSN:0040-3709
DOI:10.1002/tera.1420480308
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1993
数据来源: WILEY
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8. |
Relationship between abnormal somite development and axial skeletal defects in rats following heat exposure |
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Teratology,
Volume 48,
Issue 3,
1993,
Page 259-266
Joyce M. Cuff,
Gary L. Kimmel,
Carole A. Kimmel,
Dinorah J. Heredia,
Natalie Tudor,
Judy Chen,
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摘要:
AbstractThe effects of in vivo heat exposure on gestation day (GD) 10 rat embryos were evaluated on GD 11 to determine the relationships between morphological sequelae following in vivo and in vitro exposures and between effects detected on GD 11 and those observed in postnatal day (PND) 3 pups. Anesthetized rats were exposed to 42°C in a warm air incubator until their rectal temperatures reached 41°C or until a rectal temperature of 42–42.5°C had been maintained for 5 minutes. Heat‐exposed embryos exhibited a significant decrease in growth parameters including head length, somite number, and protein content/embryo versus controls. These changes correlated well with in vitro effects from an earlier study (G.L. Kimmel et al., '93). Among the morphological endpoints which were slightly delayed in development were the caudal neural tube, branchial bars, forelimb and hindlimb. The only effect on the embryos that could not be explained as a transient delay in development induced by heat was the induction of unsegmented somites. Additional embryos were exposed to 42°C for 15–20 min in vitro and examined specifically for unsegmented somites, which were observed in 47% of embryos exposed to 42°C in vivo or in vitro. This phenomenon was observed in somites 9–20, i.e., those that give rise to cervical and thoracic vertebrae and ribs. These results correlated well with the axial skeletal malformations observed in PND 3 pups exposed to the same heat treatment (C.A. Kimmel et al., '93). © 1993 Wiley‐Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United St
ISSN:0040-3709
DOI:10.1002/tera.1420480309
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1993
数据来源: WILEY
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9. |
Glucose and scyllo‐inositol impair phosphoinositide hydrolysis in the 10.5‐day cultured rat conceptus: A role in dysmorphogenesis? |
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Teratology,
Volume 48,
Issue 3,
1993,
Page 267-278
P. J. Strieleman,
B. E. Metzger,
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摘要:
AbstractCulture of the postimplantation rat conceptus from gestational day 9.5–10.5 in media supplemented withd‐glucose or scyllo‐inositol decreases tissue myo‐inositol and phosphoinositides with a concomitant increase in dysmorphogenesis. A number of mitogenic agents initiate cellular proliferation and differentiation through receptors coupled to phosphoinositide hydrolysis. To test whether the decrease in conceptus phosphoinositides is associated with a reduced phosphoinositide hydrolytic response, we developed a protocol to stimulate phosphoinositide hydrolysis. Phosphoinositide hydrolysis was monitored by measurement of [3H]inositol phosphates after preincubation in serum free media. We examined the ability of serum, platelet‐derived growth factor (PDGF), epidermal‐derived growth factor (EGF), insulin‐like growth factor 1 (IGF‐1), insulin like growth factor 2 (IGF‐2), endothelin‐1 (ET‐1), and endothelin‐2 (ET‐2), to stimulate phosphoinositide hydrolysis. As measured by [3H]inositol monophosphate ([3H]InsP1) accumulation, normal rat serum, ET‐1, and ET‐2 stimulated phosphoinositide hydrolysis 47%, 420%, and 154% above the basal rate observed in serum free controls. EGF stimulated a statistically insignificant 15% increase while PDGF, IGF‐1, or IGF‐2 were without effect. We further characterized ET‐1 stimulated phosphoinositide hydrolysis. Dose‐response studies disclosed that incremental increases in [3H]InsP1(129–420%) are observed over a concentration range of 10–1,000 nM. Maximal stimulation was not reached even at 1,000 nM. Temporally [3H]InsP1and [3H]InsP3levels increased linearly during incubation periods of 15‐60 min. We further analyzed ET‐1 stimulated phosphoinositide hydrolysis in 10.5‐day conceptuses cultured for 24 hr in media containing high concentrations of glucose (23.3‐56.6 mM) or scyllo‐inositol (0.55, 5.5 mM). Under these dysmorphogenic conditions that concomitantly decrease the phosphoinositide precursor pool the response to ET‐1 was blunted 28–76% for glucose and 29–65% for scyllo‐inositol. This suggests that the effect of glucose and scyllo‐inositol on lowering phosphoinositide precursor pools also results in a decrease in the response to agonists using the inositol/lipid intracellular pathway. This impaired signaling response may contribute to initiating dysmorph
ISSN:0040-3709
DOI:10.1002/tera.1420480310
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1993
数据来源: WILEY
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10. |
Maternal substance abuse and the developing nervous system. I.S. Zagon and T.A. Slotkin (eds), Academic Press, Inc., San Diego, 1992, 377 pp., $89.95 |
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Teratology,
Volume 48,
Issue 3,
1993,
Page 279-279
Jeffrey A. Golden,
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ISSN:0040-3709
DOI:10.1002/tera.1420480311
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1993
数据来源: WILEY
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