bluuebunny/crossref_metadata_2025 huggingface dataset:
The morphology of various types of cell death in prenatal tissues
Authors: Schweichel J.‐U. , Merker H.‐J.
Published: June 2005

The morphology of physiological cell death and of necroses caused by treatment with various embryotoxic substances (cyclophosphamide, actinomycin D, vitamin A, vincristine, 6‐aminonicotinamide, 6‐mercaptopurine) and Mg deficiency were studied electron microscopically in rat and mouse embryos and fetuses. Three types of necroses were distinguished in control tissues. (1) Condensation and fragmentation of single cells undergoing phagocytosis, with lysosomal disintegration of the fragments in neighboring cells. (2) Primary formation of lysosomes in dying cells, with activation and subsequent destruction and phagocytosis of the fragments by neighboring cells. This type of cell death in most instances was found during destruction of organs and large cell units. (3) Disintegration of cells into fragments, which were optically no longer detectable, without involvement of the lysosomal system, e.g., in embryonic and epiphyseal cartilage before ossification. In cases of embryolethal toxic agents, e.g., Mg deficiency, cell necroses of large areas prevailed, which were characterized by typical pyknoses (rough, dense chromatin) and lack of lysosomes. In the case of teratogenic effects, however, substances that disturb replication, transcription, and translation (cyclophosphamide, actinomycin D, 6‐mercaptopurine) caused an increase in the number of necroses of type 1. It can, therefore, be assumed that under these conditions similar processes take place in physiological and experimentally induced necroses. After administration of vitamin A, labilization of lysosomes and necroses of type 2 were observed.
Pathology and epidemiology of conjoined twinning in swine
Authors: Selby Lloyd A. , Khalili Abbass , Stewart Robert W. , Edmonds Larry D. , Marienfeld Carl J.
Published: June 2005

Among 67 pigs with conjoined twinning observed over four and one‐half years the majority had partial rather than complete twinning. Fifty‐two percent of the 67 pigs were classified as syncephalus, i.e., with 1 head and two bodies. Epidemiologically, most were crossbred pigs born in February, March, and April on farms scattered throughout the swine‐producing regions of Missouri. In addition each was the only deformed pig in the litter. Comparison of some 32 swine husbandry variables for conjoined twin herds and matched‐paired environmental control herds did not identify any major environmental or genetic factors associated with conjoined twinning in Missouri swine.
Effects of alkaloids of Veratrum californicum on chick embryos
Authors: Bryden M. M. , Perry Clare , Keeler R. F.
Published: June 2005

Chicken eggs were treated with cyclopamine or jervine, either by yolk‐sac injection or application through windows made in the shell. Both methods resulted in a high mortality rate. No significant increase in the frequency of malformations resulted from yolk‐sac injection, but did occur after application of the compounds using windowed eggs. Retarded growth and development was also observed. Treatment with jervine at 14–28 h of incubation produced a high frequency of head malformations, but treatment later than this did not. Treatment with jervine at 30–40 h of incubation produced a high frequency of abnormalities other than head abnormalities, especially lordosis and rachischisis, whereas treatment before 28 h did not have this result. The frequency of head anomalies in the 16–28 h treatment groups was 30–60%, and the incidence of other anomalies in the 30–40 h treatment groups was 30–65%. Head abnormalities observed were cebocephaly, cyclopia, hydrocephalus, microphthalmia, meningocele, and encephalocele. Trunk and limb deformities were hemimelia, amelia, lordosis, and rachischisis. It was concluded that cyclopamine and jervine have a direct teratogenic effect on chick embryos. It appears that these compounds produce head malformations in chick and sheep embryos when they are exposed relatively at about the same developmental stage.
Teratogenic effects of cadmium in rats
Authors: Chernoff Neil
Published: June 2005

The teratogenic effects of subcutaneous injections of cadmium in CD rats were investigated. Injections of 4–12 mg/kg CdCl2 on 4 consecutive days beginning on days 13–16 of gestation resulted in a dose‐related rise in the fetal death rate, decrease in fetal weight, arid increase in the rate of anomalies. The anomalies included micrognathia, cleft palate, clubfoot, and small lungs. The lung/body weight ratios were significantly reduced in fetuses of animals injected with 8 mg/kg CdCl2 on days 14–17 of gestation. The data indicate that this was a specific retardation and not merely a reflection of differential organ growth rates and overall fetal growth retardation.
Alterations in the ontogeny and specific activity of phosphomonoesterases associated with abnormal chondrogenesis and osteogenesis in the limbs of fetuses from folic acid‐deficient pregnant rats
Authors: Jaffe Norman R. , Johnson E. Marshall
Published: June 2005

A transient maternal folic acid‐deficiency resulted in alterations in the ontogeny and specific activity of pH‐dependent phosphomonoesterases from the limbs of rat fetuses. Associated with the biochemical lesion was an anomalous pattern of chondrogenesis and osteogenesis. These results offer an explanation for the limb malformations observed in near‐term fetuses and further implicate the phosphomonoesterases in cartilage and bone development.
Epidemic waves in the prevalence of anencephaly and spina bifida in New York State
Authors: Janerich Dwight T.
Published: June 2005

This study examines the prevalence of anencephaly and spina bifida among births in New York State from 1945 through 1971. The data suggest that the regression of the epidemic that peaked in the early 1930s may be continuing. The apparent leveling of the rate during the 1950s may have been another of the epidemic waves or peaks that have occurred in the last 70 years.
Skeletal deviations in rats: Malformations or variations?
Authors: Dr. Kimmel Carole A. , Wilson James G.
Published: June 2005

Skeletal variations were studied in 20‐day rat fetuses from pregnant females given acetazolamide, actinomycin D, or sodium salicylate and in vehicle‐treated and untreated controls. A slight increase over untreated control values as regards resorptions, malformations, and certain skeletal variants was noted in some vehicle‐treated groups. Supernumerary 14th ribs were designated as rudimentary (less than half the length of the 13th rib) or extra (half or greater than half the length of the 13th rib) on the basis of actual measurement showing a bimodal distribution in length. The occurrence of rudimentary 14th ribs was highly variable after vehicle or teratogen treatment. Extra 14th ribs occurred in a dose‐related fashion after actinomycin D (days 7 and 9) and sodium salicylate (which sometimes also produced 15th ribs), but not after acetazolamide treatment. Sternebrae were variable in form after most treatments and these changes showed a slight but insignificant increase after actinomycin D or sodium salicylate on day 9. The incidence of variations of vertebral centra was highly changeable after all treatments but was consistently greater after sc treatment with water or acetazolamide and appeared to be dose related after sodium salicylate. The authors believe that none of these skeletal variants should in themselves be considered as malformations. The possibility exists that extra 14th ribs could be regarded as indicators of teratogenic potency of a drug at some higher dosage; but the data presented did not demonstrate the usefulness of the other skeletal variants examined as signals of teratogenic potential.
Questions concerning the possible association of potatoes and neural‐tube defects, and an alternative hypothesis relating to maternal growth and development
Authors: Emanuel Irvin , Sever Lowell E.
Published: June 2005

The hypothesis concerning the possible association of potatoes and neural‐tube defects has been reviewed. The bulk of epidemiological evidence presented to date fails to support this hypothesis. An alternative hypothesis is proposed for the etiology of anencephalus and spina bifida involving the interaction of three categories of causal factors: genetic, immediate, which pertains to the pregnancy in question, and intergenerational, which pertains to the growth and development of mothers of affected children. The epidemiological evidence is reviewed that supports an intergenerational concept, and includes the socio‐economic gradient, secular and geographic Variation, and migrant studies. The hypothesis is consistent with the complex epidemiological patterns that have emerged, and raises the question of the relevance of reliance on specific teratogens as the sole extragenetic explanations for these malformations. It is more likely that these defects are truly multifactorial in origin and relate to a complex interplay of biological and social factors rather than to single teratogens.
Perinatal infections and epidemiology of anencephaly and spina bifida
Authors: Kurent Jerome E. , Sever John L.
Published: June 2005

The cases of anencephaly and spina bifida occurring in the Collaborative Perinatal Study were analyzed for maternal and pediatric indices of intrauterine infections. As an extension of these studies epidemiological and clinical data from the study population were also analyzed. Review of data from serially collected maternal serum specimens for specific antibody to selected viral antigens as well as cord serum determinations of IgM provided no evidehce to suggest that perinatal infection plays a prominent role in the etiology of these malformations. The raciai distributions of anencephaly and spina bifida differed significantly in that the rate of anencephaly was six times higher in whites than blacks. On the other hand whites and blacks had approximately the same rates of spina bifida. In view of this raciai disparity the Suggestion that a single common environmental agent is responsible for both defects, as included in Renwick's ('72) hypothesis must be modified.
Autonomic drug effects on the heart rate of early rat embryos
Authors: Robkin Maurice , Shepard Thomas H. , Baum David
Published: June 2005

We examined the effect of cardioactive drugs on the heart rate of intact rat embryos at day 11 (25 somites) of gestation, the stage of development prior to cardiac innervation. Tested were the autonomic drugs methoxamine and isoproterenol, the β‐adrenergic receptor blocker propranolol, and the phosphodiesterase inhibitor theophylline. Our observations indicated that (1) methoxamine had no effect; (2) isoproterenol and theophylline caused in creases in the heart rate; and (3) propranolol inhibited the effect of isoproterenol but did not affect the response to theophylline. We concluded that our results are consistent with (1) Ahlquist's ('48) original concept of α and β adrenergic receptors and the observation that the heart has no α receptors, (2) with the role of cyclic‐AMP in the model of the adrenergic receptor proposed by Sutherland ('68), and (3) with the observations that the embryonic heart at this stage of development is not yet innervated and so is without the vagal reflex arc (Hogg, '57; Gomez, '58).
The inheritance of susceptibility and resistance to the teratogenic effect of 1‐ethyl‐1‐nitrosourea in Inbred Strains of mice
Authors: Diwan Bhalchandra A. , Meier Hans
Published: June 2005

Because the teratogenic effects of 1‐ethyl‐l‐nitrosourea (ENU) were observed to be strain dependent, a hybridization experiment was made between the susceptible C57L/J amd the resistant AKR/J strains of mice. ENU induced mortality and malformations were found to be influenced by maternal, cytoplasmically transmitted, sensitivity and resistance factors. Apparently, the C57L/J strain contributes maternal traits enhancing fetal susceptibility, whereas the AKRsol;J strain contributes resistance factors. Their nature and function are unknown but several possibilities are proposed as to how they may lead to the genetic differences observed in ENU‐induced teratogenicity.
Congenital infections due to reovirus type 3 in hamsters
Authors: Kilham Lawrence , Margolis George
Published: June 2005

Reovirus type 3 was able to induce various effects in fetuses depending on the period of gestation pregnant hamsters were inoculated. Inoculations on gestation days 1–5 resulted in a high rate of fetal deaths. Fetuses of females inoculated on days 9–11 all became infected, but survived and developed normally. Reovirus proliferated to high liters in placentas and uteruses and was recovered from amniotic fluids in higher titer than from fetuses. Presence of phloxinophilic cytoplasmic inclusion bodies in pathologic studies revealed a spectrum of fetal infection ranging from mild involvement of the epidermis and ora mucosa to widespread systemic disease involving skin, visual organs, skeletal muscle, and neural tissues as well as voluntary muscles. These findings were substantiated by immunofluorescence studies. Throughout these experiments pregnant animals remained in good health in spite of having relatively high and sustained viremias. In view of the ubiquitous distribution of reoviruses in nature, and their lack of interspecies differences, observations of their ability to induce serious transplacental infections as well as hydrocephalus in laboratory animals point to the desirability of continued study of their potential role in the etiology of human disease.
A community of human malformation syndromes involving the müllerian ducts, distal extremities, urinary tract, and ears
Authors: Pinsky Leonard
Published: June 2005

“Syndrome fever” is a term used to characterize the prolific publication of “new” human congenital malformation syndromes in the last decade. One way to manage syndrome fever, that is, to assimilate and utilize efficiently its valuable informational by‐product, is to create nosologic communities composed of member‐syndromes which have close general and specific phenotypic similarities. The phenotypic community approach to human mal‐formation syndrome taxonomy is applicable to rare, family‐specific syndromes, to well‐known syndromes that have achieved firm, independent identities, and to mixtures of the two. A community of six syndromes, four of them apparently rare, is proposed. All share uterovaginal malformation, but neither this type nor any other single type of malformation is essential for a syndrome to merit membership in the community. Five of the six syndromes have distinc‐tive and and/or foot malformations. Four of the six share malformations of the urinary tract; in a fifth urinary incontinence probably reflects a subtle dysmorphism. Three of the six syndromes have anomalies of the aural appa‐ratus; in two this involves an association between severe renal dysgenesis and middle ear ossicle defects. The sharing of similar malformations involving several systems suggests that the respective causes of the syndromes act on the same developmental pathway(S). All six syndromes have occurred in a familial distribution; four are probably determined by major mendelian genes. Malformations of the axial skeleton are rare, but those of the distal extremities are common, in the familial syndromes belonging to the group. The reciprocal tendency is found in sporadic occurrences of severe uterovaginal dysgenesis (Rokitansky‐Küster‐Hauser syndrome) and in those with so‐called nonspecific female pseudohermaphroditism.
Human symmelia: Determination of sex and other features
Authors: Monie I. W.
Published: June 2005

A specimen of human symmelia was judged at first to be a male from the appearance and disposition of the pelvic viscera but histological study of the gonads later showed that it was a female. This raises the question of whether the preponderance of males with this abnormality might be explained, at least in part, by incorrect diagnosis of sex particularly where this has been based on gross appearances. The bladder, rectum, anus, and external genitalia were missing and the kidneys were replaced by a mass of renal tissue dorsal to the lower aorta. There was a single umbilical arrery which was identified as a persistent left primary umbilical artery. Within the lower limb were two femora, two tibiae, and one fibula. Secondary centers of ossification were present in the distal ends of the femora and the proximal ends of the tibiae.
Teratogenic effects of ochratoxin A in mice
Authors: Hayes A. Wallace , Hood Ronald D. , Lee Humphrey L.
Published: June 2005

Treatment of pregnant mice ip with 5 mg/kg ochratoxin A on one of gestation days 7–12 resulted in increased prenatal mortality, decreased fetal weight (with the exception of those treated on day 9), and various fetal malformations. Exencephaly and anomalies of the eyes, face, digits, and tail were the most common defects. The most severe malformations were complete median facial clefts associated with exencephaly and eye defects. Skeletal defects also were noted involving the ribs, vertebrae, and skull.
Caudal mesoderm pattern of anomalies: From renal agenesis to sirenomelia
Authors: Källén Bengt , Winberg Jan
Published: June 2005

The use of 6168 unselected malformed infants, obtained from the Swedish Register of Congenital Malformations during the years 1965–1971, made possible an analysis of a complex of malformations that form a series from the Potter syndrome to sirenomelia. A total of 73 infants belonging to this group were identified among the approximately 550,000 births — an incidence of 1/7500 births. They formed a series from infants with the typical Potter syndrome to typical sirenomelia. Analysis of the association of various malformations indicated til at pulmonary hypoplasia and “Potter face” are not only an effect of oligohydram‐nios. A mesodermal damage is postulated as the cause of the complex of malformations. A variable craniocaudal extension of the damage can explain the different expressions of the syndrome. Closure defects of the central nervous system, facial clefts, and congenital heart defects were less common than expected when compared with other infants with multiple malformations. The incidence of these infants born in Sweden has apparently increased over the years. There was also an apparent preponderance of them in central Sweden. Pregnancies ending with the birth of infants with this malformation complex began during summertime more often than could be expected. No exogenous cause was identified.
Presence of contractile proteins in mouse fetal palate prior to shelf elevation
Authors: Lessard James L. , Wee Elizabeth L. , Zimmerman Ernest F.
Published: June 2005

The presence of the contractile proteins, actin and myosin, was sought in palates from day‐14.5 mouse fetuses in an effort to account for the mechanism of palate shelf elevation. Day‐14.5 tongues were carried through the same procedures as a positive control. The excised tissues were labeled with radioactive amino acids by culturing in vitro. After adding carrier actin and myosin it was possible to purify these components to constant specific activity using both palates and tongues. On this basis at least 2.1–3.3% of the radioactivity in the palates copurified with actin and about 3.6–4.7% copurified with myosin. Similarly, 1.8–3.9% and 2.5–3.3% of the radioactivity in the tongues purified with actin and myosin, respectively. About 70% of the radioactivly labeled component purified from both palates and tongues migrated with the carrier actin in SDS‐polyacrylamide gels indicating an identical molecular weight. In contrast the major radioactive component in the purified myosin from both tissues had a molecular weight (180,000) slightly lower than adult myosin. In addition it was possible to extract these proteins from the labeled palates in the form of ac to myosin. The possibility that the myosinlike component may represent an embryonic form and the role that these proteins might play in palate shelf movement is discussed.
Amniogenic bands as a cause of syndactyly in a young human fetus
Authors: Ornoy Asher , Sekeles Eliezer , Sadovsky Eliahu
Published: June 2005

A fetus spontaneously aborted in the 4th month of gestation is described. The fetus displayed nonsymmetrical syndactyly of both hands and partial amputation of fingers in one hand caused by a dense tissue microscopically found to be composed of multiple folds of amnion. The placenta was examined, and showed severe pathology: multiple hematomas, infarctions, and fibrosis. The possible mode of formation of amniogenic bands is discussed and correlated with the clinical history and pathology of the placenta and membranes.
Antiheart antibody production of cardiovascular malformations in the mouse: A preliminary study
Authors: Nora James J. , Miles Vincent N. , Morriss Jill H. , Joy Weishuhn E. , Nihill Michael R.
Published: June 2005

Cardiovascular malformations were produced in 17% of A/J and C57BL/6 mice using isogeneic antiheart antibody (RAMHS) and in 22% of C57BL/6 mice using allogeneic RAMHS by injecting on four consecutive days of gestation (days 8–11 or 12–15). The antiheart antibody was raised in rabbits and adsorbed against mouse kidney and liver to yield an antiserum with high antiheart activity and low activity against other organs, demonstrably kidney. Cardiovascular maldevelopment occurred in 9% of mice injected with antikidney antibody (RAMKS), 7% receiving normal rabbit serum, and 1% receiving normal saline. A highly significant (P < .001) difference between all of the RAMHS and the normal saline groups demonstrated that antiheart antibody is teratogenic to the developing heart; and a significant difference (P < .05) between allogenic RAMHS and RAMKS antibody in the frequency of induction of cardiovascular anomalies suggests that there is organ‐specific activity to antiheart antibody. The type of cardiovascular anomalies caused in the mice studied were the same (VSD in C57BL and ASD in A/J) as those that occur spontaneously or are produced by other teratogens such as dextroamphetamine. Antiheart antibody thus did not appear to produce a specific type of maldevelopment but rather made manifest the malformation to which there appears to be a hereditary predisposition (genetic‐environmental interaction).
Inhibition of palatal fusion in vitro by hadacidin
Authors: Fairbanks Mary B. , Kollar Edward J.
Published: June 2005

This study examined the effects of hadacidin, an analogue of L‐aspartic acid, on epithelial fusion, breakdown, and mesenchymal contact in explants of fetal mouse palatal shelves. Shelves from 14‐day C57BL/6Js were explanted to agar‐solidified Eagle's basal medium. Control palates grown in this medium mimicked normal closure; i.e., an epithelial seam formed, broke down, and mesenchymal contact occurred in vitro. Experimental palates were grown in this medium supplemented with 1 or 2 mg/ml hadacidin or with concentrations of L‐aspartic acid equal to or in excess of that of hadacidin. Histological observations of explants exposed to 2 mg of hadacidin for 2 days indicated that cells of the marginal epithelia became adherent to form epithelial bands, but that subsequent epithelial breakdown and mesenchymal contact did not occur. The presence of mi to tic figures in the epithelial bands and in the mesenchyme of treated explants indicated that hadacidin inhibited breakdown, and, in addition, that it did not severely suppress or debilitate all cellular activity. This observation supports the fact that explants treated with hadacidin for 2 days, when moved to control medium for an additional 2 days, were able to undergo epithelial‐band breakdown and mesenchymal penetration. Preliminary data from explants treated with hadacidin and L‐aspartic acid indicated that competitive reversal by the amino acid did not occur consistently in vitro at concentrations of the amino acid 3 times that of hadacidin.
Thiadiazole‐induced myelodysplasia in rats
Authors: Beaudoin Allan R.
Published: June 2005

Pregnant Wistar rats were injected ip with a teratogenic dose (100 mg/kg) of 2‐amino‐l,3,4‐thiadiazole hydro‐chloride (ATDA) on day 11 of gestation (sperm day = day 0). Pregnancy was terminated at various intervals following drug injection. At autopsy some embryos were dead, some severely affected, and others only mildly affected by the treatment. The neural tube was more sensitive to ATDA than was any other tissue. The first histologically observable effect of maternal ATDA treatment was embryonic cell death in the caudal end of the neural tube, 12 h after treatment. During the next 24 h additional cells in the neural tube died, as well as cells in associated ganglia and in areas of condensing mesenchyme and somites. The tissues of the tail were especially sensitive to ATDA treatment. Forty‐eight hours after treatment repair and regeneration of neural tissue was evident. At day 20, spinal cords of affected fetuses had excrescences growing from the luminal wall, rosettes, duplication of the central canal, premature termination, and disruption of normal cellular patterns. Fetuses with myelodysplasia also had short or absent tails. It is postulated that malformations resulting from maternal ATDA treatment are due to cell death caused by ATDA acting directly on embryonic cells, with the ultimate outcome depending on the number of mitotically active cells that survive treatment to continue the process of organogenesis.
Relation of mandible growth to palate closure in mice
Authors: Shih Ling‐Yu , Trasler Daphne G. , Fraser F. Clarke
Published: June 2005

The role of mandible growth in normal palate closure and the effects on the mandible of three teratogens‐—cortisone, 6‐aminonicotinamide (6‐AN), and hypervitaminosis A — during palate closure in A/J (susceptible to cleft palate induction by these teratogens) and in C57BL (resistant) inbred strains of mice were investigated. The rate of mandible growth in the control embryos of the two strains was similar during the period of palate closure. Mandible length in A/Js was greater than that in C57BLs at the initial stage of palate closure and this remained true when it was adjusted for palate stage and for body weight. The mandibles were not shortened at the beginning of palate closure by any of the teratogens in either strain. In the cortisone‐treated groups the mandibles of C57BL embryos were consistently longer than those of controls whereas the mandibles of A/J embryos did not differ from those of control embryos at comparable body weights. It is concluded that cortisone, 6‐aminonicotinamide, and hypervitaminosis‐A do not cause cleft palate by reducing the length of the mandible at palate‐closure time.
Inheritance of branchial sinuses and preauricular fistulae
Authors: Hunter Alasdair G. W.
Published: June 2005

On the basis of two families in which branchial sinus and pre‐auricular fistulas occurred together, and a review of the literature, it is proposed that the two conditions can result from an autosomal dominant gene with some‐what reduced penetrance and variable expressivity. Embryo logical considerations suggest that the mutant gene may interfere with proper obliteration of the pharyngeal clefts, whichmay lead to either or both of the two lesions. Conductive deafness may also occur as part of the syndrome.
The distalmost palmar axial triradius in children with selected types of isolated congenital heart disease
Authors: Hook Ernest B. , Aldrich Margaret , Bonenfant Richard , Desmond Ellen , Reiss Naomi P. , Weiss Sophie C. , Wolff Grace
Published: June 2005

Numerous previous reports have suggested an association of elevation of the distal axial triradius on the palm with congenital heart disease. Our investigation, however, in which the maximum atd angles of children with (isolated) congenital heart malformation were compared with the measurement in children with functional heart murmurs (controls), revealed no statistically significant difference in any of seven types of heart defects investigated. Only in males with tetralogy of Fallot was there even a suggestive (but nonsignificant) trend towards elevation of the atd angle. The fact that in our study the data were corrected for age of the subjects may account for the difference between these observations and those of some earlier reports. It appears unlikely that screening the position of the distalmost axial triradius in ostensibly normal newborn infants will be useful in predicting the subsequent appearance of signs of a congenital heart malformation, as has been suggested by other workers.
Resistance of rat fetuses to nicotine‐induced lipolysis
Authors: Mosier H. David , Capodanno Carmen C. , Li Ivy O. W. , Magruder Caroline Sue , Jansons Regina A.
Published: June 2005

Pregnant Long‐Evans rats were fed stock diets containing 50 or 100 mg/kg of added nicotine during days 10–20 or 0–20 of pregnancy. Control rats were given stock diet during days 0–20. The mean nicotine intake ranged up to 6.03 mg/kg/day. In fetuses bled on day 20 there were no differences in levels of fetal plasma triglycerides, phospholipids, and cholesterol between the experimental and control groups. In another experiment single doses of 1 mg/kg nicotine were injected ip on day 20 into pregnant rats. Plasma free fatty acids (FFA) and triglycerides were determined at time intervals up to 30 min in the fetuses and 60 min in the females. Maternal values showed significant increases after nicotine, but fetal values did not change. Fetal adrenal and fetal whole body concentrations of epincphrinc and norepinephrine were determined up to 60 min. Fetal adrenal epinephrine decreased slightly after nicotine injection then rose and remained slightly higher than the control value. After saline injection there was no decrease in fetal adrenal epinephrine but instead there was a rise to a peak value greater than after nicotine. Fetal whole catecholamine concentrations were not changed after injection. These results are compatible with an increase in adrenal epinephrine release after nicotine. The resistance to change of fetal FFA after nicotine is probably due to a resistance to epinephrine‐induced elevation of fetal FFA. The placenta may be responsible for maintaining the steady state in fetal plasma lipids.
Developmental defects in rats treated postnatally with 5‐lododeoxyuridine (IUDR)
Authors: Percy Dean H. , Albert Daniel M.
Published: June 2005

Sprague‐Dawley rats were treated sc with 100–400 mg/kg/day 5‐iododeoxyuridine (IUDR) for 5 days beginning at 1, 5, or 10 days of age. Hair and somatic growth were markedly reduced in rats given 400 mk/kg beginning at 1 day of age. Animals were examined histologically at 10 or 20 days of age. Cerebellar cortical lesions were evident after the highest dosage in animals killed at 10 days of age, but lesions were of lesser magnitude in all series killed at 20 days of age. Retinal dysplasia was observed in rats treated beginning at 1 day of age. Lesions were characterized by thinning of the retina, undulations, and rosette formation in outer retinal layers. Foci of renal dysplasia were evident in rats treated beginning at 1 day of age. Poorly differentiated glomeruli and tubules together with nests of primordial epithelial cells, indicative of impaired nephrogenesis, were located in the superficial cortex. It is known that developmental defects can occur in the cerebellum, retina, and kidney of animals infected perinatally with certain cytolytic viruses. However, these appear to be the first studies demonstrating that a halogenated uridine given to newborn animals may result in obvious renal cortical and retinal dysplasia.
Brain cavitation and micrencephaly in lambs exposed to prenatal hyperthermia
Authors: Hartley W. J. , Alexander G. , Edwards M. J.
Published: June 2005

Ewes were exposed to 44o C for 9 h daily during the last two‐thirds or last third of gestation. The body weights of lambs were significantly reduced and cavitations of the cerebral white matter were found in 75% and micrencephaly in 44% of lambs.
Teratologic effects of ethylnitrosourea on brain development in rats
Authors: Pfaffenroth Michael J. , Das Gopal D. , McAllister James P.
Published: June 2005

Wistar rats were injected iv with ethlnitrosourea (ENU) between days 14 and 21 of gestation and the offspring killed 0, 3, 6, 10, 15, 21, and 75 days after birth. The brains obtained from these animals, on macroscopic examination, revealed that ENU produced micrencephaly of variable degrees reflected predominantly in the reduced dimensions of the cerebrum and cerebellum, inversely proportional in severity to the gestational age at which ENU was administered. The degrees of micrencephaly were first evident in 15‐day‐old animals and persisted throughout adulthood.
Placental transfer of diphenylhydantoin: Effects of species, gestational age, and route of administration
Authors: Stevens Michel W. , Harbison Raymond D.
Published: June 2005

Significant quantitative differences occurred in the placental transfer of diphenylhydantoin (DPH), which were dependent on gestational age. Administration iv of [14C] DPH to pregnant rats, mice, and hamsters at various stages of gestation resulted in significantly higher concentrations of 14C in fetal tissues during early and during late gestation, around parturition, than in between, during the period of fetal morphogenesis. 14C concentration in fetal and placental tissues also varied greatly among rats, mice, rabbits, and hamsters when compared at similar developmental stages. The highest fetal concentration was found in the mice and the lowest in the rats, with no apparent correlation with maternal plasma levels in these species. Significant extraplacental transfer of 14C to fetal and placental tissues and amniotic fluid occurred in the ligated rat uterus after ip administration of [14C] DPH. Thus placental transfer of DPH varied significantly between species and with gestational age and route of administration.
Neural‐tube defects and herpesvirus type 2 — test of a hypothesis
Authors: McDonald A. D. , Williams M. C. , West R.
Published: June 2005

A latent infection in the genital tract could explain epidemiological features of neural‐tube defects. Two of these features — a strong association with socioeconomic conditions and a low incidence in Jews — are also found in carcinoma of the cervix. It therefore seemed possible that herpesvirus type 2 might be causally related to neural‐tube defects. This hypothesis was tested by estimating neutralizing antibodies to herpesvirus types l and 2 in 125 women who had given birth to a child with a neural‐tube defect (anencephaly, spina bifida, or encephalocele) and 125 women similar in age, socioeconomic Status, and parity, who had had a child without a neural‐tube defect. In the event, it was found that mothers of defective children had a lower prevalence of neutralizing antibody to herpesvirus, especially type 1, than had the mothers of normal children.
Malformations induced in offspring of crowded and parabiotically stressed mice
Authors: Hamburgh Max , Mhndoza Lorenzo A. , Rader Michael , Lang Arnold , Silverstein Harvey , Hoffman Karl
Published: June 2005

Various malformations and anomelies were induced in fetuses of mice parabiotically joined on the 6th, 7th, or 8th day of pregnancy and in fetuses of crowded pregnant mice. Mice were crowded by placing them 18/cage (dimensions 7″ × 7″ × 10″ ) on days 3–4 of pregnancy. The abnormalities included amputation of peripheral limb structures, open neural folds, exencephaly, blisters, head, face, and tail malformation, and generalized growth retardation. The hypothesis that the teratogenic and other effects were consequences of prolonged prenatal stress induced by the experimental conditions is supported by the observation that both procedures led in a short time to significant increases in mean maternal adrenal weight.
Toxicity of methylmercury in neonatal cats
Authors: Khera K. S. , Iverson F. , Hierlihy L. , Tanner R. , Trivett G.
Published: June 2005

Kittens, 4–9 days old, from untreated mothers, received oral daily doses of 0.25–1 mg/kg Hg (as CH3HgCl) for various periods. Those given 0.25 and 0.37 mg/kg exhibited no clinical toxicity. At 0.5 mg/kg one of 3 kittens developed toxicity signs after 77 days of treatment whereas the others appeared healthy after 111 and 184 days of dosing, respectively. Typical neurological signs of methylmercury poisoning appeared in all kittens after a mean of 63 days of 0.75 mg/kg and 48 days of 1 mg/kg treatment. In kittens developing toxicity signs brain Hg content was 19–26 μg/g but blood Hg content varied widely. The blood/brain Hg ratio was dose‐dependent and decreased with increasing dosage. Degenerative changes in granule cells, Purkinje cells, and cerebral neurons and distorted myelmalion in cortical hemispheres characteristic of methylmercury toxicosis were produced by all doses. The T1/2 of Hg in blood following single oral doses of CH3Hg203Cl was 32 ± 3 days in 4‐week‐old and 36 ± 3 days in 10‐week‐old kittens. The findings indicated that a higher daily dosage is required to produce clinical methylmercury poisoning in kittens than in adult cats.
Histogenesis of benign cervical teratomas
Authors: Roediger W. E. , Spitz L. , Schmaman A.
Published: June 2005

Two cases of cervical teratoma and two of “complex cyst of the thyroid” are presented with special reference to (i) association with the thyroid gland, (ii) age of presentation, and (iii) differences between hamartomas and teratomas. The authors propose, from clinical and embryological evidence, that anterior neck teratomas arise from the thyroid gland and that failure of organogenesis at an early prenatal stage is involved. These teratomas probably arise from totipotential cells of each of the three germ cell layers found in the thyroid gland.
Human potato consumption and neural‐tube malformation
Authors: Spiers Philip S. , Pietrzyk Jacek J. , Piper Joyce M. , Glebatis Donna M.
Published: June 2005

By means of introductory correspondence and telephone interviews a survey was made of the current potato consumption habits of 265 mothers of infants born with neural‐tube malformations during January 1970 to December 1972, and of 549 matched control mothers. Both the cases and the controls were obtained from the same single source—birth certificates. Renwick's hypothesis was tested by subjecting the responses to seven questions to a modified χ2 test. The results did not support the hypothesis. In all seven instances the direction of the responses was opposite to that predicted.
Ectopic ureter in dogs: Epidemiologic features
Authors: Hayes Howard M.
Published: June 2005

In a study of 54 dogs with ectopic ureter from a large clinic‐hospital population four breeds with high risk for the defect were identified (Siberian Husky, West Highland White Terrier, Fox Terrier, Miniature and Toy Poodle). Some epidemiologic features of this anomaly in dogs were similar to those in man. The breeds with excess risk may serve as models for genetic studies.
Role of uterine contraction in producing hemorrhages in rat fetuses after amniocentesis
Authors: Singh Shamer , Singh Gajendra
Published: June 2005

The uterine‐muscle relaxant isoxsuprine hydrochloride was administered to pregnant Wistar rats 30 min before amniotic‐sac puncture on day 15 of gestation. The frequency of hemorrhages in fetuses, especially in the interdigital area of footplates, was examined 1–2 h after puncture. The frequency of hemorrhages (31%) was significantly lower (P <.001) than in fetuses not exposed to the muscle relaxant (59%), probably indicating a positive role of uterine muscular contraction in inducing hemorrhages, which were previously reported to lead to limb malformations.
Reduction in frequency of fetopathic effects of caffeine in mice by pretreatment with propranolol
Authors: Fujii Takaaki , Nishimura Hideo
Published: June 2005

Although the embryopathic effects of caffeine have been established in various mammals little is known about the mechanisms involved. Speculating that caffeine teratogenicity may be linked to catecholamine release induced by this compound we attempted a prophylactic type of experiment against caffeine teratogenicity in mice by maternal pretreatment with propranolol, a β‐adrenergic‐blocking agent. Pregnant mice on day 13 of gestation were each given a single iv injection of 2.5, 5. or 10 mg/kg propranolol and five minutes later a single ip injection of 200 mg/kg caffeine. The controls received saline or either of the drugs alone. Fetuses were examined for abnormalities on day 19 of gestation. The fetoputhic effects of caffeine were significantly reduced by pretreatment with propranolol at all dosages; and it was therefore hypothesized that the β‐adrenergic actions of catecholamines caused to be released by caffeine induce fetal circulatory disturbance, which leads to fetal abnormalities.
Teratogenicity of sodium arsenate in rats
Authors: Beaudoin Allan R.
Published: June 2005

Pregnant Wistar rats were each injected once ip with various doses of sodium arsenate at one of days 7–12 of gestation (sperm day = day 0). The embryolethal and teratogenic effects of arsenate were dose dependent. The optimum dose, 30 mg/kg, produced optimal effects when injected at day 8, 9, or 10. At autopsy (day 20) the four most frequently seen soft‐tissue malformations were eye defects (anophthalmia and microphthalmia), exencephaly, renal agenesis, and gonadal agenesis. Ribs and vertebrae were the skeletal elements most susceptible to arsenate treatment. The atlas bones were rudimentary or missing in 63% of the experimental fetuses examined for skeletal defects. The results are compared and contrasted with those previously reported following arsenate treatment in hamsters and mice.
Induction of cleft palate in mice by tranquilizers and barbiturates
Authors: Walker Bruce E. , Patterson Anita
Published: June 2005

Several barbiturates and tranquilizers, individually or in combination, were injected into pregnant mice of the A/J, CD1 and C3H strains in doses sufficient to induce sedation during the expected time of palate closure. Similar treatments were given during periods of fetal development 1 or more days prior to the time for normal palate closure. Among 2074 fetuses from treated pregnant females, 308 had isolated cleft palates. The most susceptible strains were A/J and CD1; the more teratogenic drugs were phenobarbital and hydroxyzine; the most critical treatment periods were at least 1 day prior to the time the palate would normally have closed. Thus, barbiturates and tranquilizers were shown to be significant cleft palate teratogens in mice although their mechanism of action was not investigated.
Teratologic and other embryotoxic effects of β‐aminopropionitrile in rats
Authors: Barrow Mark V. , Steffek A. J.
Published: June 2005

Increased resorption rates and decreased fetal weight were produced by intubating pregnant rats with various single (35001–4000 mg/kg) or multiple (2500–3000 mg/kg) doses of β‐aminopropionitrile (BAPN) during days 8–17 of gestation. The most embryotoxic gestational intervals were those that included day 15. Resorption (55% ) and ectocardia and/or gastroschisis (16%) resulted when 2500 mg/kg BAPN was administered on days 14–15, whereas no gross congenital malformations occurred when BAPN was administered before day 14. Higher doses of BAPN, such as 5000 m/kg, resulted mainly in fetal resorptions; 2500 mg/kg or greater on day 16 caused only cleft palate in most fetuses. Severe degrees of kyphoscoliosis, bony curvatures, and exostoses at muscleinsertion sites were observed when BAPN was given after day 16. The pathogenesis of these malformations is compatible with the known biochemical effect of BAPN — inhibition of crosslinking of both collagen and elastin — and in doing so: (a) could decrease the tensile strength of the anterior chest wall or abdominal wall to produce ectocardia and/or gastroschisis; (b) interfere with palate closure; and (c) produce osteolathyritic effects late in gestation which resemble the skeletal effects caused postnatally in young weanling animals given this agent.
Human male sexual maldevelopment: Teratogenetic classification of monogenic forms
Authors: Pinsky Leonard
Published: June 2005

The monogenic forms of structural sexual maldevelopment in human males are classified from the teratogenetic point of view. One purpose of this exercise is to highlight the unique features of human male sexual maldevelopment as an area for study by human teratologists. The uniqueness lies in three facts. The “organizer” of both the morphogenetic and functional components of normal male sexual development is known. Testes of sexually maldeveloped males can be studied prospectively and retrospectively because the testis functions prenatally and postnatally. Similarly many of the tissues “organized” by the testis prenatally undergo another round of responses at puberty. These features stand in sharp contrast to the prenatal transience and postnatal elusiveness of the critical events in most other morphogenetic systems. The biochemical knowledge of sexual development is advanced: it can serve as a chemical model for the morphogenesis of other organ systems. It is possible that various monogenic forms of human male sexual maldevelopment resulting from target‐cell unresponsiveness to androgen may be analyzable in cultured skin fibroblasts by the techniques of somatic cell genetics. Morphogenesis of the male reproductive system is susceptible to deflection by mutant genes that also produce nonsexual abnormalities.
Teratogenic and cytogenetic effects of hycanthone in mice and rabbits
Authors: Sieber S. M. , Whang‐Peng J. , Adamson R. H.
Published: June 2005

Hycanthone administered daily to pregnant mice at 3 dose levels on days 61–11 of gestation produced embryolethality and a depression of fetal body weights. At 12.5 mg/kg, no teratogenic effects were observed; at 25 mg/kg, fetal malforrnations occurred, and at 50 mg/kg, more than 90% of the conceptuses were killed. When hycanthone was administered to mice as single injections on days 5–9 of gestation embryolethal and teratogenic effects appeared to be limited to days 6 and 7. In rabbits hycanthone treatment on days 7, 8, and 9 of gestation produced embryolethality at a dose of 25 mg/kg and both embryolethality and teratogenicity at 50 mg/kg. Although hycanthone depressed the mitotic Index and induced chromosomal aberrations in microcultures of blood from untreated rabbits no cytogenetic effects of the drug were observed in either adult or fetal mice and rabbits in vivo.
Comparative embryotoxicity of diphenylhydantoin and some of its metabolites in mice
Authors: Harbison Raymond D. , Becker Bernard A.
Published: June 2005

Diphenylhydantoin (DPH)‐induced embryotoxicity in mice and alteration of such action by pretreatment of mice with phenobarbital or SKF 525‐A have been demonstrated. The present work reports the effects of DPH metabolites on prenatal growth and development: diphenylhydantoic acid, 5‐(p‐hydroxyphenyl)‐5‐phenylhydantoin, and α‐aminodiphenyiacetic acid. These metabolites administered to pregnant Swiss Webster mice were less teratogenic than DPH; 87,5 mg/kg DPH induced 85% orofacial anomalies whereas equimolar dosages of the metabolites given on gestation days 11, 12, and 13 did not produce a significant incidence of these anomalies. The metabolites did not affect fetal growth and were generally less fetocidal than DPH. These results suggest that unmetabolized DPH is the active teratogen.