bluuebunny/crossref_metadata_2025_split huggingface dataset:
An analysis of fetotoxicity using biochemical endpoints of organ differentiation
Authors: Kavlock Robert J. , Chernoff Neil , Rogers Ellen , Whitehouse Douglas , Carver Brenda , Gray Jacqueline , Robinson Kathy 
Published: June 2005

AbstractThe biochemical differentiation of the brain, lungs, liver, and kidneys of the late gestation rat fetus was examined to characterize the immediate implications of retarded growth on fetal development. Initially, the normative profile of development of the brain (weight, DNA content, and protein content), lungs (weight and surfactant accumulation), liver (weight and glycogen deposition), and kidneys (weight, alkaline phosphatase activity, and protein content) was determined on gestation days 19, 20, 21, and 22 (day 1 = finding of sperm in the vaginal smear). Subsequently, five compounds known to induce fetotoxicity (chlorambucil, methyl salicylate, mirex, nitrofen, and toxaphene) were administered during organogenesis, and the effects on organ differentiation were determined in day 21 fetuses. The effects of fetal growth retardation resulting from exposure to exogenous agents were not equally distributed among the organs studied. The liver and kidney appeared more sensitive to insult by these agents than did the brain and lungs.
Muscle abnormalities associated with radial aplasia
Authors: Stephens Trent D. 
Published: June 2005

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 repositioning.
The causes of perinatal death induced by prenatal exposure of rats to the pesticide, mirex. Part I: Pre‐parturition observations of the cardiovascular system
Authors: Grabowski Casimer T. , Payne Doris B. 
Published: June 2005

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 prenatal death.
Teratogenicity of triamcinolone acetonide in rats
Authors: Rowland J. M. , Hendrickx A. G. 
Published: June 2005

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 of embryotoxicity.
Complications of pregnancy in mice exposed prenatally to DES
Authors: Walker Bruce E. 
Published: June 2005

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 characteristic.
Regeneration by dissociated adult hydra cells: A histologic study
Authors: Chun Yong H. , Johnson E. Marshall , Gabel Bradley E. G. , Cadogan Albert S. A. 
Published: June 2005

AbstractAdult Hydra attenuata with vitally stained gastrodermal cells were dissociated into their component cells which were then randomly reaggregated into pellets by low‐speed centrifugation. Representative examples of these preparations, which develop into normal adult hydra if left undisturbed, were examined fresh at low magnification and at higher magnification in fixed, stained, and sectioned specimens. The actual pellet stage lasts less than 1 hour because the adult ectodermal and gastrodermal cells rapidly sort themselves into an inner and outer layer and seem to secrete a new mesoglea immediately thereafter. The “embryo” becomes trilaminar and attains a central cavity by extruding a large amount of cellular debris at the end of the first day. At about this same time, new tentacles begin to differentiate from rapidly dividing and undifferentiated interstitial cells. Regulation of tentacle number and position occurs at the end of two days, and the body form is essentially reestablished within 60 hours by further differentiation of the hypostomes and body wall. Complete separation of the preparation into individual polyps does not occur until about 190 hours of development.
Effect of vinblastine sulfate on the growth and histologic development of reaggregated hydra
Authors: Chun Yong H. , Johnson E. Marshall , Gabel Bradley E. G. , Cadogan Albert S. A. 
Published: June 2005

AbstractIn the presence of vinblastine, the sorting of individual cells proceeded normally but mesogleal formation was delayed. The “embryo” became highly distended and failed to expel a central mass of unused or residual cells as occurs during regeneration of “embryos” that have not been treated with a test chemical. The epithelial cells became vacuolated and failed to maintain their sheetlike arrangement and attachments, although they did begin secretion of basement membrane. Interstitial cells failed to increase in number.
Regional variations in guinea pig uterine blood flow during pregnancy: Relationship to intrauterine growth of the fetal‐placental unit
Authors: Garris David R. 
Published: June 2005

AbstractThe relationship between regional variations in uterine blood flow and fetal‐placental weight/size was examined in guinea pigs possessing three pregnancy sites per horn. Pregnancy sites were localized in either the tubal, middle, or cervical third of the uterus. Throughout pregnancy, the middle uterine pregnancy sites consistently received a lower blood flow rate than did either of the other two uterine zones. The middle zone also possessed the lowest fetal‐placental weights and smallest fetuses, based on crown‐rump length measurements, of all three zones. Significant correlation coefficients were found to exist between uterine blood flow and placental weight, placental and fetal weights, and fetal weight and crown‐rump length. Experimental reduction of uterine blood flow to the tubal pregnancy site effectively induced a retardation of intrauterine fetal‐placental growth, which was comparable to that found in the middle uterine zones. These data indicate that variations in regional blood flow rates to the guinea pig uterus affect intrauterine growth of the fetal‐placental unit.
The embryotoxic effects of ultrasound exposure in pregnant ICR mice
Authors: Kimmel C. A. , Stratmeyer M. E. , Galloway W. D. , Laborde J. B. , Brown N. , Pinkavitch F. 
Published: June 2005

AbstractThe embryotoxicity of ultrasound exposure during pregnancy was investigated in DUB:(ICR) mice. On day 0 of gestation (day of plug), pregnant mice were assigned to one of five groups: cage control, sham exposed (0 W/cm2), 0.05 W/cm2, 0.50 W/cm2, or 1.00 W/cm2. Females were anesthetized on day 8 of gestation and their abdomens were shaved to assure good acoustic coupling. The animals were strapped on a lucite board and placed vertically into a distilled degassed water bath (30°C) so that the abdomen was fully submerged and centered in the axis of the ultrasonic beam. Insonation was carried out using a PZT transducer with a radius of 1.27 cm and a frequency of 1 MHz under continuous wave conditions. Each animal was placed at a distance of 25 cm from the transducer and exposed to the appropriate intensity for 120 seconds. On day 17 of gestation, the maternal animals were killed, the uterine contents were examined, and live fetuses were weighed and then shipped in cold lactated Ringer's solution from Maryland to Arkansas. Fetuses were examined on the day following maternal sacrifice for external and visceral defects and skeletons were prepared and examined subsequently. Slight but significant differences were detected between the cage control and shamexposed groups. No statistically significant changes were seen that could be attributed to ultrasound exposure, although there was a slight increase in the incidence of malformed fetuses and the occurrence of multiple malformations in individual fetuses as intensity of the ultrasonic exposure increased.
Combined embryotoxic action of toluene, a widely used industrial chemical, and acetylsalicylic acid (aspirin)
Authors: Ungváry Gy. , Tátrai E. , Lõtrincz M. , Barcza Gy. 
Published: June 2005

AbstractCFY rats were exposed to inhalation of fresh air at days 10–13 of gestation; at day 12 the dams were given 0, 125, 250, 500, or 1,000 mg/kg acetylsalicylic acid (ASA) by gavage. During the same period of gestation (days 10–13) further groups of rats were exposed to toluene at 1,000, 2,000, and 3,600 mg/m3 atmospheric concentration and were given 250 mg/kg ASA by gavage; two subgroups of animals treated with 250 mg/kg ASA in combination with 3,600 mg/m3 toluene inhalation were given 0, 2.5, or 5 gm/kg glycine 2 hours before the ASA dose. At day 21 the animals were killed and examined for teratogenic effects and histological changes. After 48 hours toluene exposure other groups of rats were treated with ASA or with ASA plus glycine (administered 2 hours earlier) on day 20 of gestation. These animals were killed 2 hours later and the salicylic acid concentration in maternal and embryonic plasma and in amniotic fluid was measured by gas chromatography. With the rising ASA doses both maternal toxicity (increased mortality, decreased food consumption, and weight gain) and embryonic toxicity (postimplantation loss, increased incidence of weight‐retarded fetuses, increased minor anomalies and malformations, decreased average weight of fetuses) increased. Toluene was found to potentiate the toxic effect of ASA and to increase both maternal and embryonic toxicity. The type of ASA‐induced minor anomalies and malformations was also found to be altered under the effect of toluene pretreatment. By raising the toluene concentration the salicylic acid level in the maternal and embryonic plasma and in the amniotic fluid was increased above the expected concentration. The mechanism of the potentiating interaction should be looked for in the depletion of the glycine pool by toluene (and its metabolites) and in the resultant increase of salicylic acid level. Increasing ASA embryotoxicity caused by toluene can be warded off by glycine administration.
Developmental toxicology of acetonitrile in the syrian golden hamster
Authors: Willhite Calvin C. 
Published: June 2005

AbstractPregnant hamsters were exposed to acetonitrile by inhalation, ingestion, or ip injection during the early primitive streak stage of embryogenesis. Inhalation of 1,800 or 3,800 ppm acetonitrile for 60 min failed to induce malformations in the near‐term offspring whereas inhalation of 5,000 or 8,000 ppm acetonitrile was associated with production of severe axial skeletal (dysraphic) disorders. One fetus afflicted with extrathoracic ectopia cordis was recovered from a dam exposed to 8,000 ppm acetonitrile. An oral or ip dose of 100–400 mg/kg acetonitrile in hamsters of equivalent gestational age also caused malformations identical to those noted following inhalation exposure. Some dams exposed to the highest concentrations or doses of acetonitrile displayed overt signs of poisoning. Multiple injections of sodium thiosulfate antagonized the mortality and signs of intoxication associated with acetonitrile treatment. Offspring of thiosulfate‐treated hamsters exposed to acetonitrile failed to exhibit the marked teratogenic response that was associated with exposure to equivalent concentrations or doses of acetonitrile alone. Elevated concentrations of cyanide and thiocyanate were detected in all tissues studied at 2.5 hr after an oral or ip dose of acetonitrile. Cyanide was liberated when acetonitrile was incubated in vitro with hamster liver slices or NADPH‐fortified hepatic microsomal preparations. The results suggested that in vivo liberation of cyanide from acetonitrile was responsible for the production of terata.
Maternal factors in cleft lip with or without palate: Evidence from interracial crosses in the United States
Authors: Khoury Muin J. , Erickson J. David , James Levy M. 
Published: June 2005

AbstractMaternal determinants of oral clefts have been documented in studies of experimental animals but not of humans. We studied maternal and paternal influences on the well‐known differences in the incidence of oral clefts between Whites and Blacks in the United States. Using United States birth certificate data for 1973–1978, we compared the incidence of oral clefts in offspring of White‐White, Black‐Black, and White‐Black couples. Because oral clefts are underreported on birth certificates, we also compared oral clefts as a proportion of all defects reported for offspring of various combinations of parental races. After adjusting for fathers race, offspring of White mothers had a higher rate of cleft lip with or without palate (CLP) than those of Black mothers (odds ratio [OR] = 2.33, P < 10−4) and a higher proportion of CLP in their reported defects (OR = 2.41, P < 10−4). This maternal race effect did not apply to cleft palate (CP), and it persisted after adjusting for mother's age, parity, and education. However, after adjusting for mother's race, offspring of White fathers did not have a higher rate or proportion of CLP or CP than those of Black fathers. The study shows that the difference in the reported rates of CLP between Whites and Blacks is due to the effect of mother's race, whereas the difference in the reported rates of CP cannot be attributed to the independent effect of mother's or father's race. The study documents the existence of maternal determinants of CLP in humans.
Suppression of morphogenesis in embryonic mouse limbs exposed in vitro to excess gravity
Authors: Duke Jackie C. 
Published: June 2005

AbstractThis paper is a report of the first investigation of the effect of excess gravity on in vitro mammalian limb chondrogenesis. Limb buds from mice of various gestational stages were exposed to excess gravity (2.6G) using a culture centrifuge. Both forelimbs and hind limbs were cultured and the development of various limb elements was scored after four to six days. The 2.6G force significantly depressed the development of limb elements when applied during the teratogen‐sensitive period of chondrogenesis. There was a proximodistal gradient of sensitivity to excess gravity in the limb with proximal structures being less susceptible than distal ones. In some cases, proximal limb elements present prior to explantation disappeared upon exposure to excess gravity. Hypergravity's teratogenic effect is assumed to operate viachanges in tension and/or pressure on the cells, accompanied by alterations in cell morphometry and membrane properties.
Dose‐response relations of palatal slit, cleft palate, and fetal mortality in mice treated with a glucocorticoid
Authors: Kusanagi Takao 
Published: June 2005

AbstractC57BL/6 (C57BL) and SWV mice were treated subcutaneously with triamcinolone acetonide in a single dose of 1.0–7.0 mg/kg on day 12 of pregnancy, and the palate of their fetuses was examined at term. In C57BL mice palatal slit occurred spontaneously and its frequency increased with increasing doses of triamcinolone. However, this defect was not seen in SWV fetuses, even when dams were treated with the doses that induced cleft palate. The frequency of cleft palate increased in both C57BL and SWV as the dose of triamcinolone increased. Fetal mortality increased in SWV, but not in C57BL, with increasing doses of triamcinolone. Dose‐response relations were analyzed by the log‐probit transformation method. In C57BL mice, the slope of the doseresponse curve of palatal slit was significantly different from that of cleft palate. In contrast, the dose‐response curves of cleft palate were similar in both C57BL and SWV; the median effective dose was significantly greater in C57BL than in SWV. The mechanism of induced palatal slit appears to be different from that of induced cleft palate; the mechanism of cleft palate induction may be the same in both C57BL and SWV. The slope of the dose‐response curve of fetal mortality in SWV mice was different from that of cleft palate; the mechanisms underlying the resorption and cleft palate responses must be different.
Congenital and hereditary anomalies in the rhesus monkeys (Macaca mulatta) of Cayo Santiago
Authors: Rawlins Richard G. , Kessler Matt J. 
Published: June 2005

AbstractDuring seven annual birth seasons, from January 1976 to July 1982, 963 infants were born in the Cayo Santiago, Puerto Rico, colony of free‐ranging rhesus monkeys (Macaca mulatta). The reproductive rate for mature females, 4 years of age and older, ranged between 74.1% and 84.7%, with a cumulative mean of 80.8% over 7 years. Live births comprised 95.3% of the total and the secondary sex ratio was 109 male to 100 female births. No twinning was observed. Aborted and stillborn monkeys represented 4.7% of all births. The percentage of stillborn females was greater than that of males (4.0% vs. 3.1%). Neonatal death, defined as mortality within 48 hours postpartum, occurred in 0.8% of the live births.Two cases of congenital abnormalities were observed. The first was an anencephalic, acranial female and the second a congenitally blind male. Both infants were born to matrilineally unrelated 7‐and 8‐year‐old multiparous females with no prior history of delivering malformed offspring. The incidence of each defect, based on 963 births, was 0.10%, with a cumulative incidence of 0.20% for all teratisms seen during the study.Multiple occurrences of a rare, nonpathological and nonlethal hereditary anomaly were also seen. Five “golden” macaques were born into two genetically distinct social groups within the last 2 years of observation. The incidence of this phenotype, based on five cases, was 0.52%, 52 times the expected rate (.01).
Prenatal diazepam: Distribution and metabolism in perinatal rats
Authors: Simmons Roy D. , Miller Richard K. , Kellogg Carol K. 
Published: June 2005

AbstractPrevious investigations have revealed that prenatal exposure to diazepam (DZ) alters brain development and behavior in the offspring of rats and mice. In order to understand how DZ may affect the developing nervous system it is necessary to examine its metabolic fate in the neonate. It is therefore the aim of this study to investigate the disposition, metabolism, and persistence of DZ in the neonate. Dams were injected s.c. with 2.5 mg/kg of 14C DZ (10 μCi/day) on days 13–20 of gestation and their litters were fostered at birth. Dams killed within 24 hours postpartum and neonates killed at postnatal days 0, 10, and 20 were analyzed for 14C activity. Brain levels (pmoles DZ and metabolites/100 mg tissue SE) were 3.4 ± 0.3 in the dam and in the neonates were 3.2 ± 0.3 (day 0), 3.4 ± 0.3 (day 10), and undetectable at day 20. Neonatal peripheral tissue 14C activity was undetectable by day 10. Brain regional analysis indicates 14C is highest in the colliculi at day 0, but not at day 10. Brain levels of DZ, oxazepam (OXA), N‐desmethyldiazepam (NDZ), and the glucuronide (GLU) determined by high‐performance liquid chromatography (HPLC), were GLU (49%), DZ (28%), and NDZ (24%) in the dam; GLU (52%), DZ (24%), and NDZ (25%) in the day 0 neonate; and GLU (32%), DZ (12%), NDZ (39%), and OXA (19%) at day 10.The distribution and metabolism of 14C DZ that persists in the neonate following prenatal exposure differs from that which occurs in the dam. The neonatal brain contains OXA and a higher concentration of 14C exists in the colliculi region of day 0 neonates when compared with maternal brain. Prenatal 14C DZ activity persists longer in the neonatal brain than in peripheral tissue but all tissue levels are undetectable at day 20. Therefore, DZ and its pharmacologically active metabolites persist longest in the neonatal brain and could therefore alter both prenatal and postnatal developmental processes. However, no drug is present in the neonate at 20 days of age and therefore could not directly affect behavior measured then or at later ages.