bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strain differences in heat‐induced neural tube defects in mice
Authors: Finnell Richard H. , Moon Stephen P. , Abbott Louise C. , Golden Jeffery A. , Chernoff Gerald F. 
Published: June 2005

AbstractNeural tube defects are common congenital anomalies affecting approximately 0.1% of liveborn infants. It is widely accepted that these disorders are of a multifactorial origin, having both a genetic and an environmental component to their development. In a study designed to elucidate the genetic factors involved in a mouse model of hyperthermia‐induced neural tube defects, it is apparent that a hierarchy of susceptibility exists among various inbred mouse strains. Female SWV mice were extremely sensitive to a 10‐minute hyperthermic treatment on day 8.5 of gestation, with 44.3% of their offspring having exencephaly. The other strains used in these studies (LM/Bc, SWR/J, C57BL/6J, and DBA/2J) all had less than 14% affected offspring. In experimental situations where the environment is held constant and the only difference between the strains in their genotype, it is assumed that the difference in response to a teratogen is genetically mediated. To test the hypothesis that several genes are involved, reciprocal crosses were made between strains of high, moderate, and low sensitivity. When this was done, the high sensitivity of the SWV strain was lost in the F1 hybrid, implying not only that multiple genes are involved, but that it is the embryo's genotype and not the maternal genotype that is the major factor in determining susceptibility to heat‐induced neural tube defects.
Major limb malformations following intrauterine exposure to ethanol: Two additional cases and literature review
Authors: Pauli Richard M. , Feldman Paula F. 
Published: June 2005

AbstractTwo children are reported in whom major limb malformations were identified and whose mothers had consumed large quantities of alcohol in the first trimester of pregnancy. In one there was complete amelia of the upper limbs, while the other had preaxial polydactyly of both hands. These cases, taken together with previously reported instances of major limb anomalies following intrauterine ethanol exposure, as well as animal investigations that have demonstrated virtually identical limb malformations following ethanol administration, suggest that maternal ethanol abuse may be causally related to these limb malformations. We suggest that interruption of blood supply to the developing limb may be caused by ethanol exposure and may result in all of the various limb malformations described.
Atelencephalic microcephaly in a 21‐week human fetus
Authors: Siebert Joseph R. , Warkany Josef , Lemire Ronald J. 
Published: June 2005

AbstractAtelencephalic microcephaly, a rare and extreme disorder, is known morphologically by only six cases. Derivatives of the telencephalon are absent or dysplastic, while more caudal structures are normal or mildly deformed. A more extensive form, aprosencephaly, involves structures of the diencephalon and may be associated with holoprosencephalic facies. Extracranial anomalies may be present in both atelencephaly and aprosencephaly. We describe the seventh and youngest specimen, a 21‐week female with atelencephaly. Maternal and gestational histories were unremarkable; the fetus was obtained by therapeutic abortion following diagnosis of a severe cranial malformation by ultrasound. A small and depressed, but intact, calvarium covered the brain. The forebrain was rounded and showed fused hemispheres, absent gyri, olfactory bulbs, and tracts. Caudal structures were mildly deformed. An oval mass of bone filled much of the middle cranial fossa. By light microscopy, several dysplastic changes were apparent in the forebrain. Ventricles were not present; small round cells resembling those of the germinal matrix were prominent in the forebrain. Pyramidal tracts were absent at all levels. The process responsible for these changes cannot be established with certainty; the changes are, however, in keeping with previous damage, such as that accepted for other encephaloclastic disorders. The insult in atelencephaly presumably occurs after closure of the rostral neuropore; earlier damage, with more widespread consequences, is possible for aprosencephaly. As with other destructive processes, etiology in atelencephaly and aprosencephaly is most likely heterogeneous.
Frequent occurrence of polyovular follicles in ovaries of mice exposed neonatally to diethylstibestrol
Authors: Iguchi Taisen , Takasugi Noboru , Bern Howard A. , Mills Karen T. 
Published: June 2005

AbstractThe occurrence of polyovular follicles (PF) was examined at 10‐34 days of age in the ovaries of BALB/cCrgl female mice given five daily injections of 0.1μg diethylstilbestrol (DES), 2μg DES, 100 μg progesterone (P), 137 μg 17α‐hydroxyprogesterone caproate (HPC), 20 μg testosterone (T), 20 μg 5α‐dihydrotestosterone (5α‐DHT), or oil vehicle alone starting on the day of birth, and of C57BL/Tw females given five neonatal injections of 1 μg DES, 20 μg 17β‐estradiol (E2), 50 μg 5α‐DHT, 50 μg 5β‐DHT, or the vehicle alone. Ovaries of 30‐day‐old C57BL mice given five daily injections of 1 μg DES starting at 3–25 days of age were also examined. PF incidence (% of PF per ovary) and PF frequency (% of mice with PF) were significantly greater in BALB/c mice receiving injections of DES, P, HPC, and T than in the controls. In DES‐treated mice at 34 days, PF incidence (2–13 oocytes/follicle) was 120–340 times higher than in the controls. BALB/c mice treated with T, P, and HPC showed PF incidence (two to four occytes/follicle) three‐ to six‐fold higher than in the controls. In 30‐day‐old C57BL mice treated with T, E2, and DES, PF incidence also increased by two‐ to 50‐fold. 5α‐DHT and 5β‐DHT failed to increase PF incidence. PF incidence was significantly increased only when neonatal DES treatment was begun on days 0 to 3, but was reduced when started at days 10–25. In DES‐treated C57BL mice aged 10–30 days, PF incidence was significantly higher than in the age‐matched controls.
Further characterization of the distribution and metabolism of nitrofen in the pregnant rat
Authors: Brown T. J. , Manson J. M. 
Published: June 2005

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 accumulation of nitrofen.
The embryolethality and teratogenicity of acrolein in cultured rat embryos
Authors: Slott Valerie L. , Halves Barbara F. 
Published: June 2005

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 EC50 for 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 mechanism of action in this medium.
Neural tube defects: A review of human and animal studies on the etiology of neural tube defects
Authors: Campbell L. Rebecca , Dayton Delbert H. , Sohal G. S. 
Published: June 2005

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.
Increased mortality and aneuploidy in embryos from rabbits injected with Newcastle disease virus at the time of ovulation and conception
Authors: Maroun Leonard E. , Degner Marykay , Mourey Mary Elizabeth , Rowan Dighton F. , Amankwah Kofi S. 
Published: June 2005

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 conception.
Sirenomelia and anencephaly in one of dizygotic twins
Authors: Schwaibold H. , Oehler U. , Helpap B. , Böhm N. 
Published: June 2005

AbstractThe combination of sirenomelia and anencephaly was observed in a stillborn dizygotic twin. A review of the literature revealed no other patients reported to have both conditions. Various explanations concerning the genesis of sirenomelia, and also the combination with anencephaly, are discussed.
Teratogenic effects on the CD‐1 mouse embryo exposed to concurrent doses of ethanol and aspirin
Authors: Guy Julia F. , Sucheston Martha E. 
Published: June 2005

AbstractHuman fetal alcohol syndrome characteristics have been seen in the mouse fetus by several investigators who dosed the dam with only one or two doses of alcohol. The purpose of this study was to determine if the fetal effects of acute doses of alcohol (ethanol) are altered by aspirin. CD‐1 mice were given two IP doses of a 25% v/v solution of 95% ethanol/saline (2.5 hours apart) and intubated with 250 mg/kg aspirin. The treatment regimen, begun at 8 days, 4 hours gestation, consisted of either aspirin pretreatment 1 hour before or posttreatment 1 hour after the ethanol. Control animals were treated similarly and included vehicle only, ethanol/vehicle, and aspirin/vehicle groups. One group was untreated. On gestational day 18, the dams were killed and the uterine horns were examined for live, dead, and resorbed fetuses. The live were weighed and examined for external malformations and either skeletal or visceral abnormalities. With the litter as the unit of analysis, no significant difference was found in the number of dead and resorbed among groups. There was a significant difference (P <.01) in average fetal weight in the aspirinpreteated group. When the total number of fetuses affected was considered, the aspirin pretreatment group showed significantly (P <.05) more external and visceral malformations. The skeletal examination revealed a significant (P <.05) difference in anomalies plus delayed ossification in both groups treated with the aspirin/ethanol combination. No significant differences were seen in any category in the groups receiving aspirin alone or ethanol alone. These results indicate and additive effect of aspirin and ethanol on the developing CD‐1 mouse fetus.
Teratology studies of ametantrone acetate in rats and rabbits
Authors: Petrere Judith A. , Kim Sang‐Nam , Anderson John A. , Fitzgerald James E. , De La Iglesia Felix A. , Schardein James L. 
Published: June 2005

AbstractAmetantrone acetate is an antineoplastic drug chemically described as 1,4‐bis [[2‐[(2‐hydroxyethyl)‐amino]ethyl]amino]‐9,10‐anthracenedione diacetate salt. The drug has activity against leukemia and solid tumors in animal models. The purpose of this study was to investigate the teratogenic potential in pregnant rats and rabbits when administered during the critical period of organogenesis. Daily doses of 1.5, 3.0, and 6.0 mk/kg were administered IP to pregnant rats on days 6 through 15 of gestation, and 0.2, 0.4, and 0.8 mg/kg to rabbits on days 6 through 18. Dose‐related weight loss occurred in both species during treatment as well as in the entire gestation period. Maternal and fetal parameters were evaluated upon uterotomies in rats on gestation day 20 and rabbits on day 28. In both species, there was dose‐related blue discoloration of abdominal viscerae and of skin at injection sites. In rats, fetal malformations and developmental variations were comparable between treated and control fetuses. However, the incidence of fetal malformations was increased in rabbits given 0.4 and 0.8 mg/kg but not at 0.2 mg/kg. Based on these data, ametantrone was considered teratogenic at dose levels of 0.4 mg/kg and above in rabbits.
Prevention of polydactyly manifestation in Polydactyly Nagoya (Pdn) mice by administration of cytosine arabinoside during pregnancy
Authors: Naruse Ichiro , Kameyama Yoshiro 
Published: June 2005

AbstractMale mice heterozygous for the dominant polydactyly gene Pdn (Polydactyly Nagoya) were crossed with normal or heterozygous females of the same strain. Pregnant females were treated with 5 mg/kg of cytosine arabinoside (Ara‐C) on day 12 of gestation. The offspring were removed on day 18 of gestation and examined for external malformations, and the fore‐ and hindlimbs were examined by means of bone‐ and cartilage‐stained cleared specimens.In +/+ x Pdn/+ matings, Pdn/+ fetuses, bearing preaxial polydactyly of the distal phalangeal type in the hindlimb and deformity of the 1st digit in the forelimb, were obtained in about 50% of the nontreated group. In treated fetuses, however, the incidence of polydactyly and deformity of the 1st digit decreased to 1.4 and 10.1%, respectively. Nontreated Pdn/Pdn fetuses exhibited preaxial polydactyly of the duplicated or triplicated metacarpal/metatarsal type both in the fore‐ and hindlimbs. In the treated Pdn/Pdn fetuses, the number of preaxial extra digits decreased in both limbs. Some hindlimbs of the treated Pdn/Pdn fetuses exhibited five metatarsals, normally.In the vitally stained specimens at 6 and 24 hours after injection of Ara‐C, preaxial marginal necrotic zones (fMI) were observed in almost all of the treated embryos from +/+ × Pdn/ + matings. However, approximately half of the embyros did not exhibit fMI in the nontreated control group at the same stage. Those embryos deficient in fMI were regarded as Pdn/ +.These findings indicated that a subteratogenic dose of Ara‐C prevented the genetic expression of polydactyly in almost all Pdn/+ and some cases of Pdn/Pdn mice. In addition, the fMI had an important role in the morphogenesis of preaxial polydactyly of distal phalangeal type in Pdn/+ mice.
Effects of the volatile anesthetic halothane on fertilization and early development in the sea urchin Lytechinus variegatus: Evidence that abnormal development is due to polyspermy
Authors: Hinkley Robert E. , Wright Brent D. 
Published: June 2005

AbstractThe volatile anesthetic halothane, when present at fertilization, dose‐dependently increases the incidence of abnormally developing sea urchin embryos at the first cell division. Microscopic examinations of eggs stained with aceto‐orcein or the DNA fluorochrome bisbenzimide and direct observations on isolated sperm aster complexes show that halothane induces polyspermy (multiple sperm entry) when present at fertilization. Experimental evidence suggests that anesthetic‐induced polyspermy involves impairment of both the fast (electrically mediated) and slow (morphological) blocks to multiple sperm entry. These observations clearly show that relatively brief exposures to halothane at fertilization cause polyspermy and that this effect is almost certainly responsible for the ensuing abnormal development observed at the first cell division.
6‐mercaptopurine‐induced alterations in mineral metabolism and teratogenesis in the rat
Authors: Amemiya Kenjie , Keen Carl L. , Hurley Lucille S. 
Published: June 2005

AbstractThe relationship between 6‐mercaptopurine‐induced alterations in mineral metabolism and the teratogenic effects of the drug were investigated. Pregnant Sprague‐Dawley rats were fed diets containing 4.5, 100, or 1,000 μg Zn per 1 g diet. On day 11 of gestation, dams were given intraperitoneal injections of 6‐mercaptopurine (27.5 mg/kg). At term, dams fed the 1,000‐μg Zn per 1 g diet showed fewer drug‐induced deleterious effects on reproduction and embryogenesis than did those fed lower levels of zinc. Mineral analysis of maternal and fetal tissues revealed pronounced effects of 6‐mercaptopurine on metabolism of zinc, copper, iron, calcium, and magnesium. The results of this study indicate that 6‐mercaptopurine teratogenesis may be due in part to drug‐induced changes in mineral metabolism.
Distribution, metabolism, and fetal uptake of pentavalent arsenic in pregnant mice following oral or intraperitoneal administration
Authors: Hood Ronald D. , Vedel‐Macrander Ginger C. , Zaworotko Michael J. , Tatum Fred M. , Meeks Robert G. 
Published: June 2005

AbstractPregnant CD‐1 mice were treated with 20 (i.p.) or 40 (p.o.) mg/kg sodium arsenate on gestation day 18 (plug = day 1). Individual fetuses, pooled placentas and maternal blood, urine, liver, and kidneys were obtained from three or more litters at intervals up to 24 hours following treatment. Acid‐digested samples were analyzed for total arsenic by hydride generation atomic absorption spectrophotometry. The rate of arsenic elimination from maternal samples was not influenced by administration route. First‐order elimination followed a brief period of distribution, and the biological half‐life was approximately 10 hours. Arsenic was found in most samples, with mean peak concentrations expressed as μg As/gm (wet wt.) or /ml (values listed are post‐treatment sampling times in minutes or hours and concentrations for i.p. and for p.o. treated groups, respectively) as follows: fetuses–2, 3.5; 6, 0.8, placentas–2, 9.3; 1, 2.3, blood–10 minutes, 6.9; 1, 2.0, urine–1, 712; 2, 342, kidney–20 minutes, 25.4; 1, 11.0, liver–0.5, 7.9; 1, 11.7. By 24 hours, arsenic levels in fetuses and placentas had declined to 0.22 μg/gm and 0.74 μg/gm for i.p. and 0.33 μg/gm and 0.57 μg/gm for p.o. treatments, respectively. Fetal arsenic uptake and loss were more rapid following i.p. than p.o. treatments, and although the i.p. dose was only half that used p.o., peak fetal As+5 was almost fivefold higher following i.p. treatment. These results agree with the finding that oral dosing of pregnant mice with arsenate has less effect on the conceptus than does treatment by injection. Arsenic metabolites (mono‐ and dimethyl arsenic) were quantitated in fetuses and ranged up to 83% of total fetal arsenicals by 24 hours.
Studies of the effect of 0.4‐Gy and 0.6‐Gy prenatal X‐irradiation on postnatal adult behavior in the Wistar rat
Authors: Jensh Ronald P. , Brent Robert L. , Vogel Wolfgang H. 
Published: June 2005

AbstractThirty‐four pregnant Wistar rats were X‐irradiated on the 9th or 17th day of gestation at a dosage level 0.4 Gy or 0.6 Gy or were sham‐irradiated. All mothers were allowed to deliver their offspring, and litters were limited to a maximum of eight on day 2. On day 30, 224 offspring were weaned and raised until 60 days of age, at which time testing began. Each rat randomly received, in random order, three of the following six behavioral tests: Water T‐maze, Conditioned Avoidance Response, Forelimb Hanging, Activity Wheel, Swimming, and Open Field. There were no statistically significant differences between the irradiated and control groups for maternal weight or weight gain or mean litter size, although the litter size of the 17th day 0.6‐Gy group was slightly lower. Among offspring irradiated with 0.6 Gy on the 17th day, 3‐day‐old neonates' weights were significantly reduced. Offspring irradiated on the 17th day with 0.6 Gy exhibited higher Conditioned Avoidance Response 5th‐day and retest avoidance scores than did the controls. There were also significant sex differences in responses within the irradiated and control groups for several tests, which were unrelated to radiation exposure. The results of this study indicate that low‐level X‐irradiation during the fetal period of rat gestation results in neonatal growth retardation and subtle behavioral alterations that may be manifested in adult life. Growth retardation may be the most sensitive indicator of suble effects that result from low‐level prenatal exposure to X‐rays.