bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative distribution and metabolism of triamcinolone acetonide and cortisol in the rat embryomaternal unit
Authors: Rowland J. M. , Althaus Z. R. , Slikker W. , Hendrickx A. G. 
Published: June 2005

AbstractTriamcinolone acetonide (TAC) is teratogenic in rats while cortisol has been reported as not teratogenic. The objective of this investigation was to determine whether this difference in teratogenicity could be due to a difference in the metabolism and distribution of the parent compound in the embryomaternal unit. 3H‐TAC and 14C‐cortisol were administered intramuscularly to pregnant rats on day 12 of gestation. These dams were killed at each of the following time points after injection: 0.5, 1, 3, 6 and 24 hr. Maternal plasma and embryos were analyzed by high performance liquid chromatography (HPLC) and liquid scintillation counting. The plasma concentration of parent TAC was significantly greater than that for parent cortisol at all time points. The plasma elimination half‐life for TAC, 86 min, was also calculated to be significantly longer than that for cortisol, 8 min. Furthermore, the percentage of total plasma radioactivity representing HPLC resolved TAC was much higher than that representing cortisol at all time points. The concentration of TAC in the embryos was significantly greater than for cortisol at all time points. The elimination half‐life for unchanged TAC in the embryos was 142 min compared to 22 min for cortisol. The percentage of total radioactivity in the embryos representing unchanged TAC was similar to that found in maternal plasma while the percentage of total radioactivity representing unchanged cortisol was much lower than that found in maternal plasma. These findings support the hypothesis that differences in the distribution and metabolism of the parent compound are a critical factor in determining the teratogenicity of that compond.
Mirex‐induced fetal cataracts: Lens growth, histology and cation balance, and relationship to edema
Authors: Rogers John M. , Grabowski Casimer T. 
Published: June 2005

AbstractThe effects of mirex on growth, histology, and K+ and Na+ concentrations of the fetal lens are examined. Pregnant Long‐Evans rats were intubated with 6 mg/kg/day mirex in peanut oil on days 8–15 of gestation. Control dams received pure peanut oil. Fetuses were removed on days 18–21 and rated for extent of lens opacification and degree of edema. Lenses were removed, weighed, and assayed for K+ and Na+. Selected eyes were examined histologically. Cataracts were found in 49.6% of live treated fetuses on day 20, and the incidence and severity of cataracts were both correlated with the degree of fetal edema. Lens weights were reduced in treated litters whether or not cataracts occurred, but the reduction in cataractous lenses was greater. Sodium tended to be elevated and K+ reduced in lenses from treated fetuses, and the K+/Na+ ratio was significantly reduced in all treated groups. Histologically, treated lenses had swollen fibers on day 18 and areas of apparent cell breakdown by day 20. The swollen lens fibers, reduced K+/Na+ ratios and the correlation with edema suggest that fetal cataraots induced by mirex may be due to lens fiber cell breakdown subsequent to osmotic swelling.
Gross anatomical studies of a newborn with the Meckel syndrome
Authors: Pettersen James C. 
Published: June 2005

AbstractA male infant with the Meckel syndrome was studied anatomically. The findings were compared with those from eight trisomy‐13 cases to determine whether or not the superficial similarities between the two syndromes were matched by similarities in the internal variations. Emphasis was on the head and limbs.In the head, major differences were found in the nasal bones, mandible, and tongue. In the limbs, the skeletal variations were more severe in the Meckel syndrome infant, but he lacked the muscle variations diagnostic of trisomy 13.
Effects of the cytostatic drug cis‐platinum on the developing neocortex of the mouse
Authors: Köpf‐Maier Petra , Merker Hans‐Joachim 
Published: June 2005

AbstractThe effects of the new cytostatic drug cis‐diamminedichloro‐platinum(II) (cis‐platinum) on the developing neocortex of NMRI mouse embryos or fetuses were investigated using light‐ and electron‐microscopic methods. Single doses of 20 mg cis‐platinum/kg were applied intraperitoneally on day 10, 11,…, or 16 of gestation. After treatment on day 10 or 11—i.e., during the phase of organogenesis—no morphological alterations could be detected in the neuroepithelium. However, after treatment on day 12 or later, the mitotic activity was markedly reduced and a great number of cells had become necrotic within 12–24 h after application of the drug. At the ultrastructural level, the development of necroses began with a condensation of the chromatin, culminating in the formation of large condensation plaques and shrinkage and fragmentation of the cytoplasm. The observed necroses can be classified according to Schweichel and Merker as type I necroses. It is argued that the apparent teratogenic inefficiency of cis‐platinum on days 10 and 11 of murine pregnancy is caused by the inability of cis‐platinum to pass the placental barrier at this stage of pregnancy.
Phencyclidine exposure and the developing mouse: Behavioral teratological implications
Authors: Nicholas J. Michael , Schreiber Eric C. 
Published: June 2005

AbstractThe effects of perinatal exposure to phencyclidine (PCP) on the reflex development of the offspring of mothers given PCP during gestation and/or lactation were determined. ICR Swiss mice received daily injections of either PCP (5, 10, 20 mg/kg, PO) or saline during gestation and/or lactation. Thus, four groups of animals were studied; those exposed only prenatally, postnatally, both pre‐ and postnatally, or control. After birth, these offspring were observed daily until weaning for the appearance of certain reflexes, using a modification of the Fox battery. There was a delay in the disappearance of the cross extensor reflex and delayed appearance of reflexes, such as walking, crawling, vibrissal placement and vibrissal stroking in the offspring of PCP‐treated mothers. Treated animals also showed slower righting times than control animals. Growth rate was decreased in PCP‐exposed animals beginning at 3 days of age and continuing through 15 days of age. These results indicate that PCP exposure during gestation or nursing adversely affects the development of behavioral reflexes in mice and suggest that regular observation of reflex ontogeny in neonates may be a sensitive indicator of behavioral teratology.
Toxic effects of sodium selenite on pregnant mice and modification of the effects by vitamin E or reduced glutathione
Authors: Yonemoto Junzo , Satoh Hiroshi , Himeno Seiichiro , Suzuki Tsuguyoshi 
Published: June 2005

AbstractToxic effects of sodium selenite (SS) on dams and/or conceptuses and modification of the effects by vitamin E (VE) or reduced glutathione (GSH) were investigated in pregnant mice during late gestation. Dose‐dependent fetocidal effects and fetal growth retardation were observed in mothers injected SC with SS on day 12 but not on day 16 of gestation. On day 12, abortion occurred only at a dose level of 58.8 μmol/kg SS, whereas on day 16 it occurred at two dose levels: 27.2 and 40.0 μmol/kg SS. Pregnant mice were treated with or without VE (50 mg/kg, SC, daily from day 7 to day 11) and injected with a single dose of SS (46.2 μmol/kg, SC) on day 12. VE prevented abortion and maternal death, but none of the other effects such as fetal loss, fetal growth retardation, and decrease in body weight gain of the dams. Pretreatment with GSH (0, 2, or 5 mM/kg, SC) 20 min before SS injection on day 12 exacerbated maternal death, abortion, and decrease in body weight gain of the dams. No effect were observed in the number of live offspring, and in body weight of offspring.
Comparative teratogenic effects of methyl salicylate applied orally or topically to hamsters
Authors: Overman Dennis O. , White John A. 
Published: June 2005

AbstractMethyl salicylate was administered topically to pregnant hamsters at 7d9h and the teratogenic results were compared with those obtained following oral treatment with the same compound. Both treatments produced the same defect in embryos recovered at day 9: failure of fusion of the neural tube, especially in the area of the developing brain. Analysis of serum salicylate levels following both treatments produced similar curves and indicated that teratogenic levels of salicylate can reach the maternal circulation after topical exposure.
Mevalonate supplementation in pregnant rats suppresses the teratogenicity of mevinolinic acid, an inhibitor of 3‐hydroxy‐3‐methylglutaryl‐coenzyme a reductase
Authors: Minsker D. H. , MacDonald J. S. , Robertson R. T. , Bokelman D. L. 
Published: June 2005

AbstractMevinolin is a fungal metabolite, and in the hydroxyacid form, mevinolinic acid, it is an inhibitor of 3‐hydroxy‐3‐methylglutaryl‐coenzyme A (HMG‐Co A) reductase, an enzyme essential in cholesterol biosynthesis. Oral administration of 800 mg/kg/day of mevinolin to rats from days 6 through 17 of gestation produced fetal malformations of the vertebrae and ribs in 29% of the litters, and there was a treatment‐related increase in the incidence of gastroschisis. Mevinolinic acid at 60 and 90 mg/kg/day also produced fetal malformations of the vertebrae and ribs, and these teratogenic manifestations were markedly suppressed by coadministration of the product of HMG‐Co A reductase, mevalonic acid, at a dosage level of 500 mg/kg b.i.d. A diet supplemented with 0.5% or 1.0% cholesterol had no effect on the teratogenicity of mevinolinic acid. Teratology studies in rats with a dihydroxyheptanoic acid derivative of mevinolin, a compound 1/700 as potent as mevinolinic acid as an inhibitor of HMG‐Co A reductase, and dihydromevinolinic acid, an inhibitor of this enzyme comparable in activity to mevinolinic acid, indicated that the teratogenicity of these compounds was related to their relative enzyme inhibitory activity. The dihydroxyheptanoic acid derivative was not teratogenic at doses as high as 150 mg/kg b.i.d.; in contrast, when dihydromevinolinic acid was administered at 50 and 100 mg/kg/day, its potency as a teratogenic agent was comparable to that of mevinolinic acid. These studies demonstrated that inhibitors of HMG‐Co A reductase produced terata in rats and that the teratogenic effects could be antagonized by coadministration of the enzyme product, mevalonic acid.
The chronology of somites in rat embryos
Authors: Vickers T. H. 
Published: June 2005

AbstractTo establish their chronology in rats the somites of 902 embryos were counted. They were the products of 89 pregnancies terminated at three hourly intervals from 231 hours to 288 hours and then six hourly until 324 hours. Somites form at a virtually constant rate of one somite per 1.87 hours. This is incorporated in the regression equation

where y = number of somites, x = hours of gestation from 06.00 on the morning after overnight mating. The greatest variation in the maturity of embryos within any time‐determined sample was nine somites (= 16.8 hours) and the least was three somites (= 5.6 hours). Some uses for the data in experimental teratology are suggested.
Cephalothoracopagus syncephalus: A case report with previously unreported anatomical abnormalities and chromosomal analysis
Authors: Delprado W. J. , Baird P. J. 
Published: June 2005

AbstractA case of cephalothoracopagus conjoined twins is presented. The abnormality was detected antenatally by the use of ultrasonography. A detailed anatomical description is given, including previously unreported abnormalities of the cerebrum and genito‐urinary tract. Chromosomal analysis was also performed. This showed a pericentric inversion of one chromosome 9 in the fetus. Studies performed on the mother showed pericentric inversion of both chromosome 9s. A comparison of this case with previously reported cases in the literature is then given.
Increased susceptibility to 6‐aminonicotinamide‐induced cleft lip of heterozygote Dancer mice
Authors: Trasler Daphne G. , Kemp Dorothy , Trasler Tessa A. 
Published: June 2005

AbstractDancer heterozygotes (Dc/+) very rarely have cleft lip and show a dancing behaviour due to inner ear defects while homozygotes (Dc/Dc) have cleft lip. Males of the two genotypes Dc/+ and +/+ were mated to C3H strain and R stock females and Dc/+ males to Dc/+ females. On day 10/8 of gestation females were treated with 6‐aminonicotinamide (6AN) at either 19 mg/kg or 28.5 mg/kg followed 3 h later by a protective dose of nicotinamide. Controls were untreated. Both 6AN treatments caused a significant increase in cleft lip to between 25% and 29% for crosses of Dc/+ males to C3H and R females whereas crosses with +/+ males gave 0% cleft lip. In the controls the cleft lip frequency was: for Dc/+ × Dc/+ 14%, Dc/+ × C3H 1.4%, and for the other three crosses 0%. The four crosses given the high dose of 6AN and the +/+ × C3H and Dc/+ × R cross at the low dose showed significantly increased resorption rates to between 23% and 47% over the control rates of from 5% to 11%. The presence of the Dc gene increased the susceptibility to cleft lip caused by 6AN.
Agenesis of the penis, scrotal raphe, and anus in one of monoamniotic twins
Authors: Berry Susan A. , Johnson Dana E. , Thompson Theodore R. 
Published: June 2005

AbstractSevere defects in the development of the caudal axis are rare, but lead to profound consequences for the fetus. They result from damage to multiple germ layers at a very early stage of development and vary in severity depending on the timing and degree of insult incurred. One of a set of identical male twins presented with persistence of the primitive cloaca with an absent phallus and anal atresia, but normal limb development. This combination of penile agenesis, imperforate anus, and absence of the scrotal and perineal raphae is an ominous physical finding indicative of severe renal anomalies, which in all cases have been incompatible with extrauterine survival. This constellation of findings, of which our patient is only the sixth reported example, probably results from a primary defect in caudal mesoderm migration before the fourth week of gestation. In this case, the defect may have occurred as a consequence of monochorionic monoamniotic monozygotic (MZ) twinning.
Genetic microcephaly in a pair of monozygous twins
Authors: Fried K. , Micle S. , Goldberg M. D. 
Published: June 2005

AbstractA pair of monozygotic female twins with true primary microcephaly is described. The autosomal‐recessive nature of the disease is supported by the following: the twins are concordant for the disease; the parents, themselves normal, are related; the reduced skull dimensions were noted at birth; neurologic problems are absent; the karyotype is normal; the gestation and delivery were normal, without any history of influences capable of inducing microcephaly. A detailed dermatoglyphic study is given.
Sensitive stages and dose‐response analyses of palatal slit and cleft palate in C57BL/6 mice treated with a glucocorticoid
Authors: Kusanagi Takao 
Published: June 2005

AbstractC57BL/6 mice were treated subcutaneously with triamcinolone acetonide in a single dose of 2.5–15.0 mg/kg once on days 6–15 of pregnancy (vaginal plug = day 0) and the palate of their fetuses was examined at term. The sensitive stages of palatal slit and cleft palate induction were studied and dose‐response relations on days 9 and 12 of pregnancy were analyzed by the log‐probit transformation method and compared. The test of significant increase in the frequencies of palatal slit and cleft palate showed that the sensitive period of palatal slit began earlier and ended later than that of cleft palate. On day 9 of pregnancy, the slope of the palatal slit response was similar to that of the cleft palate response, but the median effective dose of the former was lower than that of the latter. The slope of the palatal slit response was similar on days 9 and 12; however, the median effective dose was significantly greater on day 9. By contrast, the slope of the cleft palate response on day 12 was significantly different from that on day 9. The results of these doseresponse analyses suggest that the underlying mechanism may be the same in palatal slit induction on days 9 and 12 and in cleft palate induction on day 9; the mechanism underlying the cleft palate response on day 12 is different from that of the other three responses, and there is more than one mechanism for cleft palate induced by triamcinolone.
Direct fetal injections of diethylstilbestrol and 17β‐estradiol: A method for investigating their teratogenicity
Authors: Henry Ellen C. , Miller Richard K. , Baggs Raymond B. 
Published: June 2005

AbstractThe synthetic estrogen, diethylstilbestrol (DES), causes urogenital malformations in humans, primates, and rodents. This study was designed to determine whether these effects of DES are related to its estrogenicity. Therefore, DES (0.1, 1, and 10 μg) or the natural estrogen, estradiol (E2) (10 and 100 μg) was injected directly into day 19 rat fetuses. In the 6‐ to 7‐week‐old female offspring exposed to DES, a dose‐related incidence of cleft phallus, hypospadias, and incomplete coiling of oviducts was observed. The single fetal injection of E2 elicited similar urogenital malformations, but was approximately 100‐fold less potent than DES. A single subcutaneous dose of either DES (0.025, 0.25, or 2.5 mg/kg) or E2 (2.5 or 25 mg/kg) to dams on day 19 of pregnancy induced a spectrum of malformations similar to that following fetal injection. The offspring of treated dams, but not those injected directly as fetuses, had nonfunctioning ovaries (no corpora lutea) yet vaginal signs of estrous were present. It is concluded that DES can act directly in the fetus and its teratogenicity does not require maternal mediation. Since a high dose of E2 produced similar malformations when given to fetuses, it appears that excess estrogen during prenatal life is teratogenic. Thus, at least those endpoints of the teratogenicity of DES that were measured are accounted for by its estrogenic activity.
Arteriovenous malformations of the brain: A teratologic challenge
Authors: Warkany Josef , Lemire Ronald J. 
Published: June 2005

AbstractCongenital arteriovenous malformations of the brain are lesions which are well‐known to neurologists and neurosurgeons but are puzzling to teratologists because they occur sporadically and are unassociated with congenital malformations outside the central nervous system. They are recommended to teratologists as a field of etiologic and pathogenetic research.
Neck web and congenital heart defects: A pathogenic association in 45 X‐O Turner syndrome?
Authors: Clark Edward B. 
Published: June 2005

AbstractThis study explores the association between neck web and congenital heart disease in patients with Turner syndrome. Of 193 cases with documented 45 X‐O karyotype, 106 (55%) had a web neck and 87 (45%) had a normal neck. The incidence of congenital heart disease was significantly different between these two groups, occurring in 30% of those with web neck and 9% of those with normal neck (χ2 = 12.82, P<.0005). The difference was most striking in coarctation of the aorta for which the prevalence was 25% with web neck and 3% with normal neck (χ2 = 17.65, P<.0001). The association between web neck and congenital heart disease suggests a pathogenic relationship exists between the two. The following hypothesis is proposed to explain the association. Increased lymphatic pressure associated with jugular lymphatic sac obstruction distends the thoracic ducts, which compress the ascending aorta altering intracardiac blood flow. Redirection of intracardiac blood flow produces coarctation of the aorta and other defects in the spectrum of left heart obstruction. This proposed mechanism is an example of a teratogenic event remote from the heart, which alters cardiovascular morphology.
Effects of ethanol on the primitive streak stage mouse embryo
Authors: Nakatsuji Norio , Johnson Kurt E. 
Published: June 2005

AbstractRecent studies of mouse models have suggested that malformations associated with the fetal alcohol syndrome (FAS) are caused by the effects of ethanol on early embryos during gastrulation and neurulation. A study of Xenopus laevis embryos showed that exposure of gastrula stage amphibian embryos to ethanol inhibits migration of the mesodermal cells, causes formation of small neural plates, and subsequently causes hypoplastic craniofacial malformations in tadpoles. We now report effects of ethanol on the primitive streak stage mouse embryos. An ethanol solution (25%) was injected intraperitonealy twice into mice of 6.5–7.0 days of pregnancy at a dose of 0.015 ml/gm of body weight. Histological and morphometric examinations of 7.5‐day embryos, 20 hr after the second injection, showed that the epiblast layer was disorganized and shrunk with formation of many blebs. In addition, formation of the mesodermal cell layer was retarded in the ethanol‐treated embryos, suggesting that exposure of gastrula stage embryos to ethanol causes similar abnormalities in mouse and Xenopus embryos. These results suggest that the inhibition of the morphogenetic movements during gastrulation may be the primary effect of ethanol in causing major craniofacial malformations of FAS.
Estrogenic activity of zearalenone and zearalanol in the neonatal rat uterus
Authors: Sheehan Daniel M. , Branham William S. , Medlock Kevin L. , Shanmugasundaram E. R. B. 
Published: June 2005

AbstractFusarium sp. contaminated feedstuffs elicit adverse estrogenic effects in several commercially important animal species via the mycotoxin zearalenone. An estrogenically active synthetic derivative, zearalanol, is used as an anabolic agent in cattle. Since estrogens can irreversibly alter target tissue development, we investigated the estrogenic activity of these compounds in the neonatal rat uterus. Both induced dose‐dependent premature uterine growth when injected daily on postnatal days 1–5 (ED50 = 1.3 mg/kg BW). Nuclear estrogen receptor levels dramatically increased 1 hour after either a single injection on day 5 or after five daily injections. In 5‐day‐old animals, the translocated nuclear receptor was characterized as a single class of binding sites with a dissociation constant (KD) for estradiol (E2) of 1 nM. At 15 days, zearalanol‐treated animals showed greater uterine nuclear receptor retention than zearalenone‐treated animals. In 5‐day‐old animals, single mycotoxin doses induced five fold elevations of ornithine decarboxylase (ODC) at 6 hours. Unlike the growth response, ODC dose‐response studies showed zearalanol to be about 20‐fold more effective than zearalenone. Time course studies revealed that a low dose of zearalenone, but not of zearalanol, resulted in a shift in peak activity from 6 to 8 hours. These data suggest that metabolism of zearalenone may be important in short‐term pharmacodynamics. In a competitive binding assay, neither compound competed [3H]E2 from the E2 binding site on alphafetoprotein. We conclude that the uterine growth response and ODC induction demonstrate the neonatal estrogenic action of these mycotoxins, apparently mediated via the estrogen receptor. The greater effectiveness of zearalanol in inducing ODC may be related to nuclear retention and/or zearalenone metabolism.