bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cryptorchidism, an epidemiologic study with emphasis on the relationship to central nervous system dysfunction
Authors: Depue Robert H. 
Published: June 2005

AbstractThis case‐control study examines the relation of cryptorchidism to central nervous system dysfunction. Elevated odd ratios were found for cerebral palsy (RR = 34), low IQ (RR = 2.7), and low motor function measured by the Bayley test (RR = 3.6). Low IQ and cerebral palsy were independent risk factors for cryptorchidism. Breech labor (RR = 2.6), a gestation < 34 weeks (RR = 2.0), and being a twin (RR = 4.1) were also independent risks. Other risk factors were estrogen use by the mother (RR = 3.3) and a maternal Quetelet index < 24 (RR = 1.6). All of these risks were statistically significant. These factors suggest that cryptorchidism may be caused either by sex steroid action directly on the testes or by CNS damage, which in turn causes suppression of pituitary gonadotropins. The increased occurrence of cryptorchidism in twins and small babies indicates that retarded general fetal development can be another mechanism for maldescent of the testes.
Acetazolamide: Maternal toxicity, pattern of malformations, and litter effect
Authors: Holmes Lewis B. , Kawanishi Hiroaki , Munoz Alvaro 
Published: June 2005

AbstractThirty litters of C57BL 6J mice were administered intraperitoneally one of four doses (0, 500, 750, and 1,000 mg/kg maternal weight) of acetazolamide on day 9 of gestation. The fetuses were removed on day 18 and fixed, stained, cleared, and examined for the pattern of malformations. The forelimb postaxial limb deficiency was the most common abnormality, but forelimb postaxial polydactyly and a postaxial deficiency in the hindlimb were also observed. Males were significantly more likely to be malformed than females at all doses, in contrast to the predominance of females observed in rat fetuses exposed to acetazolamide (Scott et al.: Teratology 6:239–240, '73). The occurrence of limb malformations did not correlate with maternal weight loss, the birth weight of the fetus, or the position of the fetus in the uterus. A “litter effect” was demonstrated in that there was a nonuniform distribution of litters with different proportions of malformed fetuses.
Secalonic acid D‐induced changes in palatal cyclic AMP and cyclic GMP in developing mice
Authors: Eldeib Mohamad M. R. , Reddy C. S. 
Published: June 2005

AbstractSecalonic acid D (SAD) induces cleft palate in the developing mouse by an unknown mechanism. To investigate possible roles of cyclic nucleotides (cAMP and cGMP) in the teratogenesis of SAD, cAMP and cGMP levels were measured in the extracts of fetal palates of gestational age 130 through 1612 (dayshours). Fetuses were obtained from pregnant CD‐1 mice treated on day 110 of gestation, with either 5% (wt./vol.) sodium bicarbonate (NaHCO3, control) or 30 mg/kg of SAD in 5% NaHCO3, intraperitoneally (i.p.). Radioimmunoassay was used to quantitate cyclic nucleotide levels. Cyclic AMP levels peaked on day 1412 of gestation in controls. In the SAD group there was a significant decrease in cAMP levels on days 1312 and 140 of gestation and a decrease of 30% in total cAMP on days 130 through 140 of gestation, with little or no change at the peak on day 1412. On day 1512, however, the SAD group had a 68% increase in palatal cAMP level over the control. Control levels of cGMP appeared to follow a diurnal pattern reaching maximal levels at the end of the dark cycle. In contrast, SAD decreased the cGMP level by 31% on day 1312 (P < 0.05) and increased it 100% above that of the control level on day 150 (P < 0.01). Total cGMP during days 150 through 1612 of gestation was 33% higher than control (P < 0.01). The number of clefts in the SAD group was significantly higher at all points following palate closure in the control fetuses (140 through 1612) with values ranging from 20% to 34% versus 0% in the control (P < 0.01–0.005). Morphological changes on days 130 through 150 indicated a failure of shelf elevation in middle and posterior palatal regions of SAD‐treated fetuses. These results suggest that the induction of cleft palate by SAD is associated with dynamic changes (initial decrease followed by later increase), in vivo, in established cyclic nucleotide patterns and support a mechanistic role for cyclic nucleotide‐mediated cellular processes in normal as well as abnormal palate development.
Postnatal uterine development in the rat: Estrogen and antiestrogen effects on luminal epithelium
Authors: Branham William S. , Zehr David R. , Chen James J. , Sheehan Daniel M. 
Published: June 2005

AbstractWe examined the effects of the synthetic estrogens, diethylstilbestrol (DES) and ethynylestradiol (EE), and the triphenylethylene antiestrogen, clomiphene citrate (CC), on uterine growth and development in the rat. These compounds, unlike estradiol, do not bind significantly to rat serum alphafetoprotein (AFP). Administration of DES or EE during the period of normal uterine gland genesis (postnatal days 10–14) induced luminal epithelium hypertrophy and increased uterine wet weight. The durations of these responses were dose‐related. By day 26, luminal epithelium cell numbers were significantly depressed, compared to controls. Uterine gland development was delayed 6 to 9 days, depending upon estrogen dose, and the numbers of uterine glands ultimately achieved were generally less than in untreated control animals. While a daily dose of 0.1 μg CC/rat did not alter uterine development, 10 μg CC/rat caused prolonged luminal epithelium hypertrophy and inhibited uterine gland genesis without inducing the large increases in uterine weight or the decreases in luminal epithelium cell number seen after estrogen exposure. The number of stromal cells was significantly increased on day 26 after CC exposure. Together with previous studies, these data demonstrate the greater potency and developmental stage specificity of non‐AFP‐bound estrogens with respect to altering uterine gland development. In addition, these data suggest that the disruptive influence of antiestrogens on gland genesis may be mediated through an indirect influence on the uterine stroma.
Halothane prevents nitrous oxide teratogenicity in Sprague‐Dawley rats; folinic acid does not
Authors: Mazze Richard I. , Fujinaga Masahiko , Baden Jeffrey M. 
Published: June 2005

AbstractThe teratogenic effects of nitrous oxide (N2O) administered with halothane or folinic acid (FA) were studied in two separate experiments using a total of 206 timed‐pregnant Sprague‐Dawley rats. In each experiment, rats were exposed to either 1) air (n = 30–40); 2) N2O (50–75% for 24 h on day 8 of pregnancy, n = 20–30); 3) test agent (i.e., 0.27% halothane for 24 h on day 8 of pregnancy; or 5 mg/kg/day of FA on day 5–13 of pregnancy, subcutaneously by osmotic pump, n = 20–30); or 4) N2O + test agent (n = 20–30). Cesarean sections were performed on day 20, and fetuses were examined for visceral and skeletal abnormalities. There were no differences in pregnancy rate, number of implantations and live fetuses per rat, and fetal weight among any of the groups. Treatment with N2O resulted in significantly higher incidences of resorptions and of major visceral and minor skeletal abnormalities. Halothane administered with N2O protected against these effects; folinic acid did not. Using an additional 65 nonpregnant rats, hepatic methionine synthase activity was measured after treatment with 50% N2O, 50% N2O plus 0.27% halothane, or 50% N2O plus 5 mg/kg/day of folinic acid. Methionine synthase activity was equally depressed in all groups. These findings do not support the commonly held theory that inactivation of methionine synthase is the sole cause of N2O teratogenicity; rather, they suggest a multifactorial etiology, which may include changes in uterine blood flow.
Distribution of mercury 203 in pregnant rats and their fetuses following systemic infusions with thiol‐containing amino acids and glutathione during late gestation
Authors: Aschner Michael , Clarkson Thomas W. 
Published: June 2005

AbstractTo investigate the effect of amino acids and the tripeptide glutathione (GSH) on tissue uptake of methylmercury (MeHg) in the developing rat fetus in utero, pregnant rats were continuously infused into the external jugular vein with 0.1 mM L‐cysteine, 0.1 mM L‐leucine, 0.1 mM GSH or saline commencing on day 17 of gestation. This was followed at 24, 48, and 72 hours by external jugular infusion of 50 μM [203Hg]‐MeHgCl administered in 1 ml over 1 hour. Pups were surgically removed from the uterus on gestational day 21. Whole body, brain, kidney, liver, and placental 203Hg radioactivity was measured by means of gamma‐spectrometry. Brain 203Hg concentration in pups exposed in utero to L‐cysteine was significantly higher compared with pups exposed to saline (P <0.05). Brain 203Hg concentration in pups exposed in utero to L‐leucine and GSH was significantly depressed compared with pups exposed to saline (P <0.05). Kidney 203Hg concentration was not significantly changed in all treatment groups compared with controls. Liver 203Hg concentration was significantly depressed in L‐leucine‐ and GSH‐treated pups compared with controls (P <0.05). Placental 203Hg concentration was not affected by any treatment compared with controls. These effects occurred despite no difference in total 203Hg body burden among pups, irrespective of the treatment. In addition, infusion with L‐cysteine resulted in a significant increase in 203Hg brain concentration in dams compared with controls, and 203Hg brain concentration in L‐leucine‐ and GSH‐treated dams was significantly depressed compared with controls. Thus 203Hg distribution in both adult and developing animals is altered by chronic amino acid or GSH infusions and suggests that MeHg uptake may be mediated through the formation of a cysteine‐MeHg complex which is transported across the blood‐brain barrier by the neutral amino acid carrier transport system.
Embryotoxic and teratogenic effects of aluminum nitrate in rats upon oral administration
Authors: Paternain Jose L. , Domingo Jose L. , Llobet Juan M. , Corbella Jacinto 
Published: June 2005

AbstractIn order to determine the embryotoxic and teratogenic potential of aluminum, pregnant Sprague‐Dawley rats were treated by gavage with a daily dose of 180, 360, or 720 mg/kg of aluminum nitrate from the sixth through to the fourteenth day of gestation. Fetal examinations were performed on day 20. The number of corpora lutea, total implants, and resorptions as well as the number of live and dead fetuses in the treated animals were not significantly different from the control group. Therefore, embryolethality of aluminum cannot be induced (as a measure of percent dead and resorbed fetuses). However, exposure of rats to aluminum nitrate resulted in decreased fetal body weight and increased the incidence and types of external, visceral, and skeletal malformations and variations in all the treated groups. Consequently, teratogenic effects of aluminum‐nitrate administration may result in rats given high oral doses that induce concomitant maternal toxicity.
Central nervous system malformations induced by triamcinolone acetonide in nonhuman primates: Pathogenesis
Authors: Tarara R. P. , Wheeldon E. B. , Hendrickx A. G. 
Published: June 2005

AbstractThe pathogenetic sequence for TAC‐induced encephalocele is in agreement with hypotheses proposing that neural tube closure is followed by protrusion of the mesencephalon, with subsequent growth and development resulting in herniation of the cerebrum and cerebellum. This model could serve to clarify the pathogenesis of encephalocele and to stimulate further study in comparing this defect to other dysraphic states. Triamcinolone acetonide (TAC) was administered intramuscularly (10 mg/kg) to 16 pregnant rhesus monkeys (Macaca mulatta) for 5 alternate days of pregnancy, beginning on gestational day (GD) 23. Conceptuses were removed by hysterotomy at GD 35, 42, 50, or 70 and examined grossly and histologically. Length, area, and perimeter of the tectum and aqueduct area and perimeter were measured with an image analyzer. Changes in treated specimens were suggestive of forces within or ventral to the tectum resulting in dorsal protrusion, rostral‐posterior stretching, and attenuation. The angle of the cephalic, pontine, and cervical flexures was also measured. The more acute angle of the cephalic flexure and less acute cervical flexure of treated specimens could represent altered orientation secondary to a mesenchymal deficiency. However, the less acute angle of the pontine flexure in treated specimens suggests an intrinsic alteration in the neural tube. This suggests that encephalocele may result from a combination of mesenchymal and neural tube abnormalities.
Changes with gestational age in the nutritional requirements of postimplantation rat embryos in culture
Authors: Cockroft D. L. 
Published: June 2005

AbstractRat embryos explanted at 9.0, 9.5, and 10.5 days of gestation were cultured for periods of 61, 49, or 45 h, respectively, in extensively dialysed rat serum supplemented with various combinations of glucose, amino acids, and vitamins. Glucose was found to be a necessary and sufficient energy source for embryos of all three ages, and virtually no development took place in its absence. Only the youngest embryos required free amino acids for good development in dialysed serum, whereas at all three ages, vitamin supplementation was necessary. However, lack of vitamins had a much more marked deleterious effect on the younger embryos than on those explanted at 10.5 d. Experiments with media deficient in individual vitamins showed that for normal development, 9.0‐d embryos required a number of vitamins—principally pantothenic acid, riboflavin, inositol, folic acid and niacinamide, whereas 10.5‐d embryos needed only riboflavin. For embryos explanted at 9.5 d, the position was intermediate, with riboflavin and inositol the most significant vitamins. Inositol deficiency in embryos explanted at 9.5 d produced a characteristic neural tube defect—failure of closure at the level of the hindbrain. Thus it appears that both the range of micromolecular nutrients and the severity of developmental impairment in their absence decrease with advancing gestational age.
Teratological assessment of exposure to time‐varying magnetic field
Authors: Stuchly M. A. , Ruddick J. , Villeneuve D. , Robinson K. , Reed B. , Lecuyer D. W. , Tan K. , Wong J. 
Published: June 2005

AbstractA teratological assessment was performed using rats that were exposed to an alternating magnetic field. The magnetic field had a sawtooth waveform similar to that produced by video display terminals (VDTs). Female rats were exposed 2 weeks prior to and throughout pregnancy at a rate of 7 h/day. Three intensities of magnetic field (5.7, 23 or 66 μT) were used. All of these field intensities were much greater than those to which VDT users are exposed. A slight but statistically significant decrease in maternal lymphocyte count for the highest intensity field was found as compared with the control group. However, the lymphocyte count was within the normal range, and the observed changes in hematological parameters were considered mild. No other maternal or fetal parameters that were examined showed a significant difference for any of the three field intensities. Where minor variations in skeleton, development were observed they were known to be the common “noise” that appears in every teratological evaluation.
Alterations in cell surface galactosyltransferase activity during limb chondrogenesis in brachypod mutant mouse embryos
Authors: Elmer William A. , Pennybacker Mark F. , Knudsen Thomas B. , Kwasigroch Thomas E. 
Published: June 2005

AbstractThe autosomal mutation brachypod (bpH/bpH) in the mouse affects the development of precartilage mesenchymal condensation in the limb‐bud. We have previously shown that this defect is localized to the expression of terminal N‐acetylglucosamine (GlcNAc) glycoproteins in the plasma membrane (Elmer and Wright, '83). The present study is focused on cell surface galactosyltransferase (GalTase), an ectoenzyme that transfers galactose to its GlcNAc substrate. Purified plasma membrane preparations derived from wild‐type ( +/+ ), heterozygote (+ /bpH) and brachypod (bpH/bpH) embryonic mouse limb cells were assayed for GalTase activity during in vitro and in utero chondrogenesis using High‐Performance Liquid Chromatography (HPLC). On embryonic day E12, prior to overt expression of the mutant gene, no significant difference in GalTase activity was observed. By the third day in culture, all major chondrogenic elements of the autopod were present in +/+ and +/bpH embryos, whereas the mutant autopods were markedly deficient in staining and appeared consistently shorter. The accumulation of alcianophilic cartilage matrix in the wild‐type was accompanied by a 29% increase in GalTase activity, which reflected the net change (29%) observed during development from days E12 to E13 in utero. The GalTase activity for the in utero E13 mutant (13%) was significantly different from control. In culture, day E12 mutant autopods actually decreased in their GalTase level by 3 days so that the activity was reduced to only 57% of the wild‐type. Though GalTase activity in the heterozygote showed an intermediate expression, optical image analysis did not reveal consistent differences in cartilage development when compared to +/+, arguing against a gene‐dosage effect at the gross anatomical level. These data indicate that an increase in plasma membrane GalTase activity is a natural developmental event that occurs during limb‐bud chondrogenesis and a decrease in GalTase activity contributes to the dysmorphogenesis in brachypod limb‐buds.
Chondrodystrophic mice with coincidental agnathia: Evidence for the tongue obstruction hypothesis in cleft palate
Authors: Clarke Laura , Hepworth W. Bradford , Carey John C. , Seegmiller Robert E. 
Published: June 2005

AbstractMice homozygous for either of two mutations, chondrodysplasia (cho) or cartilage matrix deficiency (emd), have short‐limbed chondrodystrophy. This phenotype includes retroganthia, relative macroglossia, and cleft palate. It has been postulated that the cleft palate in these mice is the result of tongue obstruction during palatogenesis. Agnathia associated with microglossia is an independent spontaneously occurring defect in the strains bearing these mutations. The coincidental occurrence of agnathiamicroglossia with chondrodystrophy lends itself to the study of the mechanism of cleft palate formation. We examined approximate midsagittal histological sections of normal and chondrodystrophic newborn mice, both with and without agnathia. Mandibular measurements and examinations of palate closure and tongue structure were made from photographic prints. Typical chondrodystrophic mutants with cleft palates had a mean mandibular length that was 66% of normal and a tongue that appeared large relative to the shortened mandible. Chondrodystrophic mutants with agnathia and microglossia had a mean mandibular length that was further reduced to 30% of normal, yet had a closed palate. We also observed two nonagnathic chondrodystrophic mutants that had slightly decreased mandibular lengths, microglossia, and closed palates. These observations suggest that tongue obstruction during palatogenesis is the pathogenetic mechanism of cleft palate in chondrodystrophic mice. A similar tongue obstruction hypothesis has been proposed as the mechanism of cleft palate formation in the human Pierre Robin sequence, which consists of retrognathia, glossoptosis, and cleft palate. This mechanistic hypothesis has been challenged, but our findings support the tongue obstruction hypothesis in the Robin cleft.
Intrauterine herpes simplex virus infection
Authors: Baldwin Steven , Whitley Richard J. 
Published: June 2005

AbstractNeonatal herpes simplex virus (HSV) infection usually is the consequence of intrapartum infection, with disease onset between 5 and 15 days of life. More recently, intrauterine HSV infection has been identified. Intrauterine infection is apparent within the first 24–48 hr of life and is associated with skin vesicles/scarring, chorioretinits, and/or hydraencephaly. The recognition that babies with these findings can have disease caused by HSV should prompt enhanced physician awareness in the evaluation of newborns with suspected intrauterine infection. The frequency of intrauterine infection appears to be about 5% of all babies with neonatal HSV infection.
Cadmium exposure on day 12 of gestation in the Wistar rat: Distribution, uteroplacental blood flow, and fetal viability
Authors: Saltzman Risa A. , Miller Richard K. , di Sant'Agnese P. A. 
Published: June 2005

AbstractThe effects of cadmium exposure (40 μmole CdCl2/kg, s.c.) on day 12 of gestation were evaluated in the Wistar rat. At 16–18 hours following such cadmium exposure, blood flow (as determined by radiolabeled microspheres) to the chorioallantoic placenta (CAP) was significantly reduced by 35%; at 24–26 hours, blood flow to the CAP had returned to control levels and was still unaffected at 38–43 hours. Uterine blood flow was not significantly altered at any of these timepoints. Between 16–18 and 24–26 hours after cadmium exposure, the concentration of cadmium in the placenta decreased significantly, while total cadmium content did not change. By 38–43 hours after cadmium exposure, total cadmium content of the placenta had increased significantly, although cadmium concentration was unchanged. There were no adverse effects on fetal viability or growth, as determined on day 20 of gestation. In sharp contrast, near‐term (day 18) exposure to 40 or 50 μmole CdCl2/kg (s.c.) resulted in 53% and 82% mean incidences of fetolethality, respectively, within 24 hours. Administration of 50 μmole CdCl2/kg (sc) on day 12 also had no effect on fetal growth but resulted in increased fetolethality (12%). Thus midgestational cadmium exposure and its accompanying alterations in placental blood flow do not compromise fetal viability or growth. The differential response to cadmium at mid‐ and late gestation, in terms of fetolethality, is not due to maternal cadmium dose.
Developmental study of neural tube closure in a mouse stock with a high incidence of exencephaly
Authors: Macdonald K. B. , Juriloff D. M. , Harris M. J. 
Published: June 2005

AbstractAbout 17% of embryos and fetuses in the SELH/Bc mouse stock have the anterior neural tube defect, excncephaly. No other malformations are seen. The genetic liability to exencephaly was shown to be probably genetically fixed in the SELH/Bc stock. This means that SELH/Bc embryos with successful neural tube closure are genetically the same as exencephalics. Females were significantly more likely to be affected than males (66% females).The pattern of morphological development events during anterior neural tube closure on days 8 and 9 of gestation was compared among 322 ICR/Bc (normal), 304 SWV/Bc (normal), and 265 SELH/Bc embryos. Anterior neural tube closure was found to follow a strikingly different pattern in almost all SELH/Bc embryos than in either of the normal strains or in previous published studies. SELH/Bc embryos lack the initial contact between the anterior folds in the posterior prosencephalon/anterior mesencephalon region (Closure 2). In spite of this, all but 17% manage to close the anterior neural tube by extending caudally the later occurring normal anterior zone of contact and fusion at the most rostral aspect of the prosencephalon (Closure 3) through the region of Closure 2 to meet the zone of closure of the rhombencephalon, Closure 4. Anterior neural tube closure was completed late, and in some SELH/Bc embryos, elevation and fusion in the mesencephalon did not occur at all.In histological sections of six‐ and eight‐somite embryos, elevated numbers of pyknotic cells in the neuroepithelium and mesenchyme, and elevated numbers of unstained inclusions in the neuroepithelium were found; but their relationship, if any, to the abnormal pattern of neural tube closure is not clear.