bluuebunny/crossref_metadata_2025 huggingface dataset:
Kidney malformations in fetuses of A × C line 9935 rats
Authors: Fujikura Toshio
Published: June 2005

Fifty A × C 9935 strain inbred rat litters were examined near term; 88/315 fetuses (27.9%) showed renal malformations (renal agenesis and hydronephrosis). Unilateral renal agenesis occurred more often on the right side (11.5%) than the left (3.6%), especially in males. Renal agenesis was always associated with absence or hypoplasia of a uterine horn or vas deferens and epididymis on the corresponding side. However, the ovaries or testes were present and intact. Hydronephrosis was seen more often on the left side (11.4%) than the right (3.5%). There was no significant sex difference in the frequency of renal agenesis and hydronephrosis. In hydronephrosis the ureteropelvic junction was patent, and hydroureter always accompanied moderate hydronephrosis. Atresia near the vesicoureteral junction was considered as a cause of hydronephrosis. There was a close morphogenetic relation between renal agenesis and hydronephrosis.
Effects of intrauterine administration of acetazolamide in rats
Authors: Scott William J.
Published: June 2005

A technique was utilized for intrauterine deposition of acetazolamide, to study the locus of action resulting in malformations in fetal rats. A 30‐gauge needle, attached to a Hamilton microliter syringe, was inserted through the uterine wall, and acetazolamide was deposited in three different regions. Deposition in the yolk sac and/or decidua capsularis produced typical forelimb deficiency in 7/46 surviving fetuses, while injection into the exocoelom produced 2/9 typically deformed fetuses. In contrast, deposition of acetazolamide into the decidua basalis and/or chorioallantoic placenta produced only 1/46 typically deformed fetus, suggesting that the chorioallantoic placenta is not the locus of acetazolamide action. The small amount of teratogen needed to produce the typical deformity when injected in the yolk sac or exocoelom, plus the total lack of deformed fetuses from control and noninjected implantation sites, eliminated disturbance of maternal metabolism as a causative factor in acetazolamide teratogenesis.
Sex differences in the incidence of certain congenital malformations: A review of the literature and some new data
Authors: Hay Sylvia
Published: June 2005

Percentages of males with selected congenital malformations reported in a large number of studies have been tabulated and analyzed. Males more often than females have been reported to have congenital hydrocephalus, cleft lip with or without cleft palate, esophageal defects, omphalocele, anorectal defects, polydactyly, syndactyly, reduction deformities, and plantar flexion foot defects. More females have been reported to have anencephaly, spina bifida, cleft palate, simple umbilical hernia, and dorsal flexion and inward rotational foot defects. Down's syndrome has been reported more frequently in males in studies that included older patients and more frequently in females in studies restricted to newborn populations. Sources of data also appear to be related to interstudy variations in sex ratios of anencephaly, cleft lip with or without cleft palate, and isolated cleft palate. It is suggested that unequal sex‐specific risks of death (prenatal in the case of anencephaly) account for the observed variations in the reported sex ratios of these malformations.
Teratogenic effect of 6‐azauridine in rats
Authors: Gutová Marcela , Elis Jiřrí , Rašková Helena
Published: June 2005

The embryotoxic effects of 6‐azauridine, given during different periods of gestation in rats, are described. Administration on days 1–6 was lethal or without any effect. Days 6–12 was the period of greatest embryonic susceptibility. 330 and 110 mg/kg caused 100% resorption; 36 mg/kg embryolethality in 85%, teratogenicity in 53.8%. After 12 mg/kg 5.8% of the fetuses were malformed, mostly with encephalocele and gastroschisis. Administered on days 12–18, 3,g/kg was 100% embryolethal and 1 g/kg 32.7% embryolethal and 100% teratogenic, causing malformations of extremities. After 330 mg/kg 65.2% of fetuses survived without any visible damage. Following single administrations of 6‐azauridine embryolethality was commonest after 3 g/kg on days 8 and 11. The teratogenic effect was best expressed after 3 g/kg on day 15, 1 g/kg on day 13, and 330 mg/kg on day 8. Malformations observed were cleft palate, gastroschisis, and dysmelia.
Histochemical features of the notochord after experimental induction of neural overgrowth
Authors: Wilson Doris Burda
Published: June 2005

The notochord and its sheath were studied in chick embryos inwhich neural overgrowth was experimentally induced by means of prematurelydissociating the notochord from the neural tube in the region of the anteriorrhombomere. The embryos were removed at ages ranging from 3–5 days of incubation and were subjected to the periodic acid‐Schiff and alcian blue procedures,as well as to radioautography involving the incorporation of thymidme‐3 H. In theregion of dissociation the notochordal cells underwent vacuolization at an earlierstage than occurred during normal development. The vacuoles showed an earlyaccumulation of material which stained positively with PAS and alcian blue, andpycnosis likewise began at an earlier stage. Incorporation of thymidme‐3H intothe notochordal cells followed the same pattern in experimental and control embryos. The notochordal sheath became discontinuous in the region of dissociation,although the histochemical features seen in the sheath of normal embryos wereretained These results arc discussed with reference to the phenomenon of neuralovergrowth and to possible interactions between the notochord and neural tube during normal development.
The influence of trypan blue, Niagara blue 2B, and colloidal carbon on the absorption and transport of valine by rat intestinal segments
Authors: Kernis Marten M.
Published: June 2005

Trypan blue, a potent teratogen in the rat, affected the transfer of 14C‐valine between the mucisal and serosal sides of intestinal segments without actually penetrating the mucosal epithelial cells. This apparent alteration of a membrane or surface phenomenon resulted in statistically significant increases in (1) amount of valine absorbed, (2) amount of label transported per unit of intestinal wall, (3) rate of absorption, and (4) rate of transport. The less terato‐genic azo dye Niagara blue 2B and the inert colloid colloidal carbon had less effect on the system.
Morphogenesis of the palate in the baboon (Papio cynocephalus)
Authors: Bollert Joe A. , Hendrickx Andrew G.
Published: June 2005

A controlled breeding program was used to collect baboon embryos of known insemination ages. Serial sections of the palatine region of 37 embryos and fetuses from 30 to 64 days (d) (estimated fertilization age) werestudied microscopically and by graphic or wax reconstruction. One 100‐day fetuswas partially dissected. Nasal placodes appeared in Stage XIV (30 d, 4.3–6.0 mm).By Stage XVI (33–36 d, 6.9–9.0 mm) nasal pits developed. The primary palate and palatine processes were present at Stage XVII (36 d, 11.3–11.6 mm). Subsequent development produced rostrodorsal and vertical lengthening of the palatine processes. Rostrally they slanted caudomedially toward the base of the tongue, and dorsally they remained vertically oriented lateral to the tongue in Stage XXI (43–45 d, 18.3–19.6 mm). In Stage XXII (47 d, 22–24 mm) the midpalatine processesbegan to rotate to a horizontal position. By Stage XXIII (45–50 d, 25.8–28.0 mm)the rostral two‐thirds of the palatine processes were horizontally oriented cranialto the tongue. They were fusing to each other and to the nasal septum. The dorsalone‐third of the palatine processes were assuming a horizontal position by medialprojection. In the 53‐d fetuses (39.6–48.0 mm) the hard and soft palates wereformed except for the uvula, which remained divided until sometime after 64 d(63.0 mm). Epithelial remnants were not formed in the soft palate, suggestingthat this area was formed by mesenchymal merging without epithelial fusion.
Cytogenetic and teratologic studies on rats continuously infused with various doses of tritiated thymidine during pregnancy
Authors: Chaudhuri Jyoti P. , Haas Reiner J. , Schreml Wolfgang , Knörr‐Gärtner Henriette , Fliedner Theodor M.
Published: June 2005

The radiotoxic effect of continuous infusion of 3H‐TdR into rats from day 9 of pregnancy till term has been studied using 288, 576, 864, 1152, and 1440 μCi/day/rat. In the offspring impaired development, decreasing regenerating capacity, malformations, and lethality occurred and were found to be dose dependent. In general, these radiotoxic effects were significant only at higher dose levels. Chromosomal abnormalities also showed a dose dependency, which was discernible even at the lowest level of activity.
An investigation of dermatoglyphic asymmetry in rubella embryopathy
Authors: Hook Ernest B. , Achs Ruth S. , Harper Rita
Published: June 2005

Twenty infants born to mothers who contracted rubella in the first 20 weeks of gestation were compared to 20 controls with regard to dermatoglyphic pattern asymmetry on 11 regions of the hands and feet, dermatoglyphic orientation asymmetry in these regions, the measured and absolute values of the differences in location of the distal axial triradius on left and right hands, the variance of these differences, and the intraclass correlation coefficient of the position of the axial triradius on left and right hands. Within the experimental and control groups comparisons were also made between subsets matched for symmetric hypothenar patterns and between subsets of the same sex within a restricted birth‐weight range. The trends in all cases indicated that, contrary to the hypothesis, all measures of asymmetry were decreased in the rubella infants. Asymmetry thus seems unlikely to be a useful marker for a human teratogen with effects similar to those of rubella.
Conjoined twinning in rabbits
Authors: Chai C. K. , Crary D. D.
Published: June 2005

Four partially duplicated newborn rabbits were observed in 252 births in the inbred strain Y at The Jackson Laboratory within a 12‐month period. Two of these were full sibs and a third was a half sib of these two sets. This frequency is significant and highly suggestive of genetic transmission. All of the conjoined twins were posteriorly duplicated in various degrees. One was equally conjoined, two were unequal, and the fourth was polydactylous with a large intra abdominal teratoma. Abnormalities were found in both the skeleton and internal organ systems.
Prevention of teratogenic and embryocidal action of X rays by low doses of 5‐hydroxytryptamine
Authors: Srebro Z. , Bieleń E.
Published: June 2005

Pregnant rats were exposed to 200 r X irradiation on day 10 of pregnancy. 5‐Hydroxytryptamine at a dose of 1 mg/kg body weight given subcutaneously 25 minutes prior to the irradiation showed significant antiteratogenic and antiembryocidal properties. A statistically significant increase in body weight was observed in near‐term offspring of 5‐HT‐injected and X irradiated females when compared with those only X irradiated or untreated.
Spontaneous congenital developmental abnormalities observed at necropsy in a large survey of newly born dead lambs
Authors: Hughes Keith L. , Haughey Kevin G. , Hartley William J.
Published: June 2005

In a systematic necropsy study of 4408 newly born dead lambs derived from 79 flocks over two lambing seasons malformation considered sufficient to impair viability was observed in 80 carcasses. Agnathia was observed in 25 carcasses and comprised the major component of congenital lethal malformations. Lambs of both sexes were affected. Its occurrence was often associated with anotia, ear displacement, or ear malformation. Factors thought to be associated with this abnormality are reviewed and attention drawn to the lack of knowledge concerning the embryonic development of the first branchial arch and related structures in sheep. Developmental defects of the muscular and skeletal systems, central nervous system, cardiovascular system (particularly ventricular septal defects), and imperforate intestinal tract were the next most common malformations.
Teratogenic action of heterologous kidney antisera in mice
Authors: McCallion D. J.
Published: June 2005

Pregnant mice were injected ip with 0.25‐0.5 ml of either an antimouse‐, antirat‐, or antichicken kidney antiserum or a nonimmunized rabbit serum on various days of gestation, but principally days 7‐9. Both antirat‐ and antimouse‐kidney antisera crossreacted with mouse kidney but antichicken kidney antiserum did not. Both antimouse‐ and antirat‐kidney antisera were embryolethal and teratogenic in mice. Both antisera were localized by immuno fluorescence with goat antirabbit gamma globulins in the glomerular basement membrane of maternal kidneys and in Reichert's membrane and yolk‐sac endoderm of embryos. Antichicken‐kidney antiserum was not embryolethal or teratogenic in mice and the antiserum was not fixed in the maternal kidneys or embryonic membranes. The teratogenic agent(s) in rat and mouse nephrotoxic antisera, therefore, seems to be antibodies to class specific kidney antigens.
Effects of a teratogen (9‐methyl pteroylglutamic acid) on oxygen consumption by dispersed embryonic rat cells
Authors: Netzloff M. , Johnson E. M. , Kaplan S.
Published: June 2005

Pregnant rats were fed 100 mg/kg diet of the folic‐acid antagonist 9‐methyl pteroylglutamic acid on days 10, 11, and 12 of pregnancy. This regimen resulted in a markedly elevated Q02 in dispersed cells from 13‐ and 13.5 day embryos as compared with controls. Cells from embryos taken 1 day after the pregnant females had been returned to a complete ration gave Q02 values similar to those from control embryos. Addition of the antagonist to Warburg flasks containing dispersed cells from day‐13 embryos resulted in an elevated Q02 but not when the antagonist was added to cells from day‐14 embryos.
Cleft palate in rodents after maternal treatment with various lathyrogenic agents
Authors: Steffek A. J. , Verrusio A. C. , Watkins C. A.
Published: June 2005

Ingestion of diets containing 50% ground sweet pea seeds (Lathyrus odoratus) by pregnant Sprague‐Dawley rats on days 10‐20 of gestation resulted in high frequencies of fetal resorption and surviving young with various degrees of edema, forelimb flexure, angulation of the vertebral column, micrognathia, cleft palate, and other defects. Pregnant A/J mice maintained on such a diet on days 9‐18 of gestation produced offspring with cleft palate and other malformations. The lathyrus factor, β‐aminopropionitrile (BAPN), given in multiple oral doses to pregnant rats at various times during pregnancy also produced high frequencies of resorption and of young with edema, cleft palate, and malformations of vertebrae and limbs. However, when single doses of 500 mg BAPN were administered on day 15 the resorption rate was markedly reduced whereas the frequency of cleft palate was greatly increased. Three other lathyrogenic agents produced high frequencies of cleft palate in rats: 50 mg aminoacetonitrile on day 15, 400 mg D‐penicillamine on days 10‐15, and 50 mg semicarbazide on days 10‐16. The period of greatest cleft palate susceptibility with all the agents tested was day 15.
Chromosome studies in selected spontaneous abortions. IV. Unusual cytogenetic disorders
Authors: Carr D. H. , Law E. M. , Ekins J. G.
Published: June 2005

Among 372 spontaneous abortions four had chromosome anomalies that were unique in the series. Each one presented features of interest. There was one example of monosomy‐G and this was associated with apparently normal embryonic development to about the 28‐day stage. In two specimens extra chromosome material was found. In one instance it was added to the long arm of a B‐group chromosome in 44% of cells. In the other the extra material was an abnormal element of unknown origin. The fourth specimen was a 35‐mm fetus with cyclopia and D‐trisomy associated with a D/D translocation. The woman producing this abortus was a carrier of the same translocation. The literature relevant to these four unusual cases was reviewed.
Observation of palatine shelves in living rabbit embryos
Authors: Walker Bruce E. , Ross Lawrence M.
Published: June 2005

Rabbit embryos were removed from the uterus just prior to the time of palate closure, submerged in saline, and observed for evidence of shelf movement. When the tongue was displaced from between the palatine shelves the latter were not seen to move. After fixation and sectioning, the angle of the shelves to the sagittal plane was measured. This angle progressively approached that of embryos fixed in utero prior to shelf transposition when the tongue, or both tongue and lower jaw, were removed during manipulation in vivo. When the tongue was released it either returned to a position between the shelves or remained ventral to the shelves and forced them into a horizontal position. Thus there was no evidence of a pronounced intrinsic shelf force in rabbit embryos under the conditions of this experiment.
Morphogenesis of malformations in hamsters caused by retinoic acid: Relation to dose and stage at treatment
Authors: Shenefelt Ray E.
Published: June 2005

Female golden hamsters were each given a single administration of retinoic acid sodium saltat one of 20 stages in pregnancy. Retinoic acid is the carboxylic acid derived by oxidation of the hydroxyl group of retinol (vitamin A1 alcohol). It is rapidly excreted and appears to act for a short time. Near‐term fetuses were found to have more than 70 types of malformation. The incidence of each external malformation produced by several oral dosage levels at each of 15 postimplantation treatment times was determined. The incidence of each internal malformation at the fetal LD50 dose was determined. Forty types of malformation whose incidence was 10% or more at the fetal LD50 dose at some time in pregnancy were studied. Embryonic development of various structures was correlated with the critical period for production of each malformation, based on a table of normal development constructed by examining untreated embryos at 48 ages. In many cases the period during which administration of retinoic acid produced a given malformation began well before there was any morphologically identifiable precursor of the structure destined to be affected.
Effects of propranolol on the chick embryo heart
Authors: Jaffee Oscar C.
Published: June 2005

Propranolol had a negative chronotropic effect on the preneural chick embryo heart. The specificity of this effect was demonstrated by the finding that propranolol blocked the accelerating effects of isopropylnorepinephrine (Isopr) on the preneural heart. The establishment of threshold doses of both propranolol and Isopr for two preneural stages (50‐55 and 80‐85 hr) of chick embryo development provided evidence that the embryo heart became increasingly sensitive to these agents. A further increase in sensitivity was found when preneural threshold dosages of propranolol and Isopr were administered to 5‐day, presumably innervated, embryos. The finding that beta adrenergic blockers such as propranolol as well as catecholamines influence the preneural heart rate emphasizes the importance of chemical mediators in heart‐rate control during this period; further studies may aid in explaining the large increases in the preneural heart rate usually attributed to the “resetting” of the pacemaker.
Lathyrogen‐induced malformations in baboons: A preliminary report
Authors: Steffek A. J. , Hendrickx A. G.
Published: June 2005

Female baboons maintained on a timed pregnancy program were administered intramuscular, Intravenous, and oral doses of β‐aminopropionitrile (BAPN) and aminoacetonitrile (AAN) during the time of palatogenesis in this species. Resorptions, abortions, and fetuses with skeletal defects resulted. Cleft palate occurred in one set of twins following oral doses of 75 mg/kg/day AAN on days 43‐48 of pregnancy.
Effects of transitory maternal pteroylglutamic acid (PGA) deficiency on respiratory control ratios, phosphorylative capacity, and cytochrome oxidase activities of mitochondria from rat embryos
Authors: Chepenik Kenneth P. , Waite B. Moseley
Published: June 2005

Cytochrome oxidase activities and protein contents of homogenates and mitochondrial fractions of embryos from untreated and 9‐methyl PGA treated pregnant rats were determined on various days of gestation. Rates of respiration, ADP:O, and respiratory control ratios were determined with the mitochondrial fractions. The cytochrome oxidase specific activities of homogenates or mitochondrial fractions of treated embryos were similar to those of controls of the same age. However, total mitochondrial protein and cytochrome oxidase activities of the treated embryos were similar to those of controls even though the treated embryos were smaller than controls. The amount of oxygen consumed by the treated embryos was not significantly different from that consumed by controls and the ADP:O and respiratory control ratios calculated for mitochondrial fractions of treated and control embryos were not significantly different.
Skeletogenesis in insulin‐treated chick embryos. I. Anatomical and histological observations, with particular reference to the tibiotarsus
Authors: Rabinovitch A. L. , Gibson M. A.
Published: June 2005

Chick embryos were exposed to insulin early in development, and the gross and microscopic effects on endochondral ossification of the tibiotarsus were studied throughout the incubation period. The major anatomical effects were a generalized reduction in embryonic size, micromelia, and angulation of the tibiotarsus. There was a significant reduction in the growth rate of the tibiotarsus with some evidence of recovery toward the end of the incubation period. Histologically, the most striking feature of the tibiotarsus was degenerative necrosis of the epiphyseal cartilage. This involved all cartilage zones and was usually more pronounced in the proximal epiphyseal plate. The proliferative zone was compressed and poorly demarcated, and the usual arrangement of parallel rows of hypertrophic chondrocytes never resulted. Periosteal ossification, cartilage resorption, and marrow‐cavity formation were initially delayed but later progressed more rapidly than in the control tibiotarsi. Joint formation was impaired by the extension of necrotic areas and fibrous material across the joint space.
Generalized growth retardation in rats induced by prenatal exposure to methylazoxymethyl acetate
Authors: Fischer Milton H. , Welker Carol , Waisman Harry A.
Published: June 2005

Single injections to rats of methylazoxymethyl acetate on days 13 to 18 of gestation retarded the general postnatal development of the offspring and resulted in micrencephaly. The effects were most severe when the compound was administered on day 14 or 15 of gestation. At 35 days of age, body, brain, kidney, liver, spleen, and testis weights were significantly reduced, whereas at 14 days of age only the brain weights were significantly less than controls. The brain was the only organ that showed macroscopic malformations, characterized by greatly reduced cerebral hemispheres and defects in the cortical mantle. In addition, nuclear groups and fiber tracts throughout the telencephalon, diencephalon, midbrain, and cerebellum were reduced in size.
The etiology of human malformations: Insights from epidemiology
Authors: Leck Ian
Published: June 2005

The epidemiological evidence that led to the incrimination of thalidomide as a teratogen was obtained by a combination of descriptive, correlative, analytic, and experimental studies. Most surveys of the common malformations have however been purely descriptive. Their main value has been to clarify the relative importance of the parts that genotype and environment in general play in causation. For example, it now seems that liability to neural tube defects is influenced much more by environment and less by genotype than is the case for cleft lip; that whether genetic or environmental, the influences that produce most cases of these and other common defects are multiple; and that if even one of these influences could be identified and controlled, incidence might fall substantially. The future for epidemiological research in this field seems to lie mainly in developing hypotheses about these influences from the knowledge already gained in descriptive studies, and in testing these hypotheses by correlative, analytic, and experimental methods.
Viral antibodies in mothers of defective children
Authors: Lapinleimu Kaisa , Koskimies Olli , Cantell Kari , Saxén Lauri
Published: June 2005

In the years 1964‐66, 338 newborns with a total of 379 gross malformations of the central nervous system and matched‐pair controls were reported to the Finnish Register of Congenital Malformations. Blood samples and detailed maternal histories were obtained from 162 mothers of defective children and their respective controls during the first 2, postpartum months. In the analysis of maternal antibodies the experimental group did not differ in most cases from the controls. However, antibodies against ECHO 7 occurred with significantly (P < 0.005) higher frequency in the experimental group, and when high titers against ECHO 7 were compared this difference was even greater (P < 0.001). On the other hand, antibodies against Coxsackie B1 and high titers against B5 occurred more frequently (P < 0.05) in the control group.
Ethionine as a depressant of synthesis of and source of label for DNA in chick embryos
Authors: Ruddick Joseph A. , Runner Meredith N.
Published: June 2005

Four milligrams of ethionine containing 14C‐ethyl ethionine was injected into the chick yolk sac on day 4. The resulting embryos were reduced in size but without gross malformation. Studies of growth and of disposition of label showed that ethionine reduced the DNA increment and increased the specific activity of DNA during the first 24 h. During days 5‐12 the DNA content continued to fall behind that of controls while its specific activity of label from ethionine progressively increased. Elution of TCA supernates from Sephadex columns indicated that ethionine was available to the embryos during this time. Since the specific activity of the label in the protein and RNA fractions remained at relatively constant levels, label reached these fractions throughout the experimental period. The increasing specific activity of DNA indicated labeling at a rate exceeding the rate of net accumulation, and thus there was selective labeling of DNA from ethionine.
A new in vitro culture technique for rat embryos
Authors: Robkin Maurice A. , Shepard Thomas H. , Tanimura Takashi
Published: June 2005

A new technique for culturing embryos, which permits detailed observation and manipulation, is described. The method has been applied to rat embryos on day 10, 11, or 12 of gestation. Twenty‐four‐hour culture of day‐11 rat embryos resulted in nearly normal increases in somite number, and embryo length and protein increment of about half that occurring in vivo. After 24 h of culture the embryos generally were translucent and showed no apparent areas of gross tissue necrosis. Sections from representative embryos are presented. The apparatus is extremely compact and requires only about 9 ml of medium which is sufficient to support three embryos. The small volume allows the measurement of metabolites consumed or liberated with reasonable accuracy. The method permits a detailed and continuous record to be made of the heart rate and the addition of drugs to and sampling of the culture medium. The apparatus, named the PLASMOM, was used to measure the effect of changes in the ambient temperature on the heart rate of day‐11 rat embryos. The results showed a linear dependence of heart rate on temperature between 30 and 40° C.
Yearly and seasonal incidence of mongolism in Quebec
Authors: McDonald Alison D.
Published: June 2005

2398 births of children with mongolism between 1958 and 1967 in the Province of Quebec were registered—a rate of 1.86/1000 live births. This is somewhat higher than the rates of 1.6 recorded in Britain and 1.5 in Australia. Between 1948 and 1957 the total number of mongoloid births recorded was 1063 (0.9/1000 live births). Underascertainment, especially of mongols who died, was evidently the reason for this low rate. In neither 10‐year period were annual fluctuations in rate found comparable to those observed in Victoria, Australia. There was no evidence of seasonal variation in incidence nor of any increase following epidemics of infectious hepatitis in 1961–63. The findings support those of other surveys in the United States, Britain, and Italy and suggest that the Australian findings were either a chance occurrence or the result of a local phenomenon.
Iniencephaly and anencephaly with spinal retroflexion. A comparative study of eight human specimens
Authors: Lemire Ronald J. , Beckwith J. Bruce , Shepard Thomas H.
Published: June 2005

Two major groups of malformed human fetuses exhibit retro‐flexion of the cervical spine, one called “iniencephaly” and the other “anencephalfy with spinal retroflexion.” In the former there is a cranial cavity as well as uninterrupted skin covering the retroflexed region and the head. The latter has partial or complete absence of the neurocranium, and the affected region of nervous tissue is not covered with skin. This difference clearly suggests different times of onset of these two classes of malformation, although the frequent occurrence of caudal myeloschisis in iniercephaly suggests that the difference is very small. Despite this important difference these conditions have numerous morphological features in common which justify discussing them together. The present paper reviews these morphological details, based upon six specimens with anencephaly with spinal retroflexion and two with iniencephaly.
The effect of hydrocortisone on the closure of the palatal shelves in two inbred strains of mice in vivo and in vitro
Authors: Lahti Aito , Antila Erkki , Saxen Lauri
Published: June 2005

The effect of hydrocortisone on the development of the palatal processes of a resistant (CBA) and a susceptible (A) mouse strain was tested in vitro. In both strains hydrocortisone caused retardation of the fusion process, but never prevented it (as in vivo in the susceptible strain). It is concluded that the results lend further support to Fraser's hypothesis.
Skeletogenesis in insulin‐treated chick embryos. II. Histochemical observations, with particular reference to the tibiotarsus
Authors: Rabinovitch Albert L. , Gibson M. A.
Published: June 2005

Chick embryos were exposed to a teratogenic dose of insulin at 5‐½ days of incubation, and the effects on the histochemistry of the developing tibiotarsus were studied until hatching. Tests for mucopolysaccharides, glycogen, calcium, and alkaline phosphatase were used. The matrices of intact cartilage revealed no changes in mucopolysaccharide staining. The major staining differences occurred in areas of cartilage necrosis and suggested loss of sulfate from the ground substance. Chondrocytes exhibited no consistent changes in glycogen content. However, in the premature secondary ossification centers that developed in proximal and distal epiphyses the chondrocytes showed an accumulation of glycogen just before full hypertrophy. Calcification, although initially delayed, was extensive and dystrophic calcification occurred in the necrotic areas. Alkaline phosphatase as usual was associated with ossification and in experimental tissues was associated with necrotic areas and the secondary ossification sites.
LSD: No chromosomal breakage in mother and embryos during rat pregnancy
Authors: Emerit I. , Roux C. , Feingold J.
Published: June 2005

LSD (500 μg/kg/day ip) given to pregnant rats from the 7th–13th days of pregnancy produced no in vivo chromosome damage, either in maternal bone marrow or in the embryos. These negative cytogenetic results parallel the lack of teratogenicity observed under these conditions.
Does LSD induce chromosomal damage and malformations? A review of the literature
Authors: Long Sally Y.
Published: June 2005

Although there are reports of five children with limbs defects among 161 children from parents who took LSD (lysergic acid diethylamide) this review of the literature indicates that LSD does not cause chromosome breakage and that there is no strong evidence of teratogenicity in animals.
Embryotoxicity of methyl mercuric chloride in golden hamsters
Authors: Harris Stephen B. , Wilson James G. , Printz Richard H.
Published: June 2005

Injection of 8 mg/kg methyl mercuric chloride ip in hamsters on day 5, 8, or 9 of pregnancy caused some maternal deaths, a high incidence of fetal resorption, decreased fetal weight, and moderate to high rates of malformation among surviving newborns. The most common malformations were clubfoot and hydrocephalus. When 4 mg/kg of methyl mercury was injected on day 8 maternal animals and their offspring did not differ from controls. A dose of 2 mg/kg daily from days 1 through 14 of pregnancy caused increases in maternal deaths, fetal resorptions, and malformations, but fetal weight was not affected.
Postnatal effects of maternal hypercortisonism on skeletal development in newborn rats
Authors: Ornoy Asher , Horowitz Ada
Published: June 2005

Pregnant rats were treated daily by im injections of 10 mg cortisone acetate, on days 8–20 of gestation. Experimental term offspring were smaller than controls. Their long bones were smaller, but contained a higher per cent of ash, calcium, and phosphorus. Sections of the long bones revealed a thinner layer of maturing and calcifying cartilage in the epiphyses, and persistence of bone trabeculae and islets of cartilage, with reduced volume of bone marrow, in the diaphyses. During the first 2 postnatal weeks the experimental offspring gradually reached the control weight. Concomitantly there was a complete disappearance of the bone injuries, and a decrease of the ash and mineral concentration to control levels. It thus appears that cortisone acetate, after passing through the placenta, does not cause true congenital skeletal anomalies, but produces only a transient direct effect on the fetal skeleton.
“Apparent hydronephrosis” as a normal aspect of renal development in late gestation of rats: The effect of methyl salicylate
Authors: Woo David C. , Hoar Richard M.
Published: June 2005

The normal pattern of renal development late in gestation in rats involves a transient variation in growth rates. While the renal papilla is slowly and steadily increasing in length the renal parenchyma is rapidly and almost exponentially increasing in weight. This disparity in growth rates frequently results in a kidney that has an enlarged renal pelvis late in gestation; but this is only an “apparent hydronephrosis” since it disappears shortly after birth. Methyl salicylate retarded renal development, particularly growth of the renal papilla, and increased the number of both transient and permanent renal abnormalities in rat fetuses near term. Preliminary evidence suggested that if the renal papilla has reached a particular stage of development 1 day before birth, and is not accompanied by grossly apparent renal malformations, the kidney will be normal at weaning. However, at birth, kidneys with an absent renal papilla, but that appeared otherwise normal, cannot be differentiated on a gross anatomical level from those that are destined to be permanently abnormal.
Teratogenic effects of phleomycin in early chick embryos
Authors: Lee Hsin‐Yi , Cortés Jorge L. , Levin Martin A.
Published: June 2005

Effects of phleomycin on chick embryos explanted at stages 4–7 and cultured for 19–21 h were studied. Concentrations of 0.1–0.8 μg/ml had marked effects on stages 4–5 embryos, but had no appreciable effects on stages 6–7 embryos. The most specific effect was progressive degeneration of neural tube tissue with increasing concentration. Neural tube closure was inhibited in most malformed embryos, especially of stage 4. Heart, foregut, somites, and blood islands were occasionally affected. Abnormalities may have been due to mitotic failure in the affected tissues, since many cells were arrested at interphase or prophase and showed nuclear enlargement. In severely affected tissues, cells showed pycnosis and nuclear fragmentation.
Estrogen, progesterone, and chromosome abnormalities in rabbit blastocysts
Authors: Widmeyer Maxine A. , Shaver Evelyn L.
Published: June 2005

The chromosome complement of blastocysts recovered from rabbits injected with estradiol or progesterone during the time of ovum maturation or the first cleavage division was studied. One chromosome anomaly, a triploid, was found in 72 control blastocysts analyzed; two, a triploid and a 44/45 mosaic, were found in 28 blastocysts from rabbits given estradiol 1 h after mating; and two trisomies in 48 blastocysts analyzed were recovered from rabbits treated with progesterone at 4 or 20 h after mating. An increased number of small blastocysts, which could not be analyzed, was found after estradiol treatment near the time of the first cleavage division. A lower mitotic index than normal was found in whole mounts of these blastocysts.
A direct analysis of early chick embryonic neuroepithelial responses following exposure to EDTA
Authors: Daniels Eugene , Moore Keith L.
Published: June 2005

Transient exposure of chick neuroepithelial explants on Trowell‐type culture platforms to a chelating agent (EDTA) facilitated a direct study of the early sequences of presumptive malformative responses. Cerebral cortical tissues plus neuroretinal tissues with associated mesenchyme from 4 ½‐day embryos were studied on millipore tilters throughout a culture period of 120 h. Brief exposure (5–15 min) to divalent ion‐depleted media variably disturbed the organization of the neuroepithelial explants. The histological responses following subsequent culture in a complete medium included simulations of a number of CNS malformations (neuroretinal folds, rosette formations, ectopic cellular aggregations, and cellular depletions) previously produced by various teratogens. The adaptation of this procedure to the study of the response potential of the early embryonic tissues enabled delineation of the processes (the degree of interference on the adhesive mechanisms) presumably operative in the development of these malformations.
Greater sensitivity of female than male rat embryos to acetazolamide teratogenicity
Authors: Scott William J. , Butcher Richard E. , Kindt Charles W. , Wilson James G.
Published: June 2005

In a recent experiment involving administration of acetazolamide to pregnant rats a high proportion of survivors affected with the typical postaxial reduction deformity of the forelimb produced by this drug were females. A review of past experiments with this agent in this laboratory revealed that in all cases the percentage of affected females was greater than that of affected males. In some cases this difference was highly statistically significant. Thus, this most unusual agent, which produces a uniquely localized abnormality in the postaxial portion of the right forelimb, reveals another unusual effect by showing a predilection for female embryos.
6‐aminonicotinamide (6‐AN)‐induced abnormalities of the developing ependyma and choroid plexus as seen with the scanning electron microscope
Authors: Chamberlain J. G.
Published: June 2005

Ventricular surfaces in control and experimental day 13–21 rat brains were viewed with a Cambridge scanning electron microscope, Model S4 (40–30,000 X). Surfaces of ependyma and choroid plexus in offspring of pregnant females receiving the teratogen 6‐aminonicotinamide (6‐AN) showed retarded differentiation and reduced growth of microvilli and cilia; some flattened cells showed ruptured plasmalemmae.
The Saethre‐Chotzen syndrome
Authors: Kreiborg S. , Pruzansky S. , Pashayan H.
Published: June 2005

Five individuals in four generations affected with the Saethre‐Chotzen syndrome are reported. Serial roentgencephalometric data obtained pre‐ and postoperatively on the proband were compared with similar measurements on the affected mother and maternal uncle, both of whom had not had operative corrections. Similarity in skull form among the affected individuals was demonstrated. Head circumference, as an index of cranial growth or intracranial capacity, was misleading in assessing the intellectual potential of the affected adults. In contrast, cranial capacity, as measured by the modulus, was found to be more reliable.
An unusual case of sirenomelia
Authors: Kohler H. G.
Published: June 2005

A report is presented of a case of sirenomelia (symmelos). The affected infant was a partner in a monozygous monoamniotic twin pregnancy; the other twin is surviving and normal. In addition to anomalies regularly associated with sirenomelia such as bilateral renal agenesis, blind‐ending colon, severe abnormality of the bony pelvis, absence of both urethral and anal orifices, and medial position of the fibulae, the features of another syndrome were present composed of dextroposition and severe, complex abnormality of the heart, hyperlobation of lungs, and asplenia. Some aspects of this case seemed to be contrary to all experience of sirenomelia, e.g., the presence of both umbilical arteries, the absence of Potter facies, of hypoplasia of lungs, and of amnion nodosum, and the relatively long survival. This group of atypical features (with the exception of the normal number of umbilical arteries) can be explained by the fact that, unlike most other cases of sirenomelia, there was no oligohydramnios. This was so, presumably, because the normal twin maintained an adequate amount of amniotic fluid in the common amniotic sac.
Corticosterone‐induced isolated cleft palate in A/J mice
Authors: Hackman Robert M. , Brown Kenneth S.
Published: June 2005

Corticosterone was administered sc daily on days 11–14 to pregnant A/J female mice, 5 mg producing 80% isolated cleft palate, 2.5 mg, 31%, and 1.25 mg, 6%. The prenatal death rate was not increased by corticosterone in litters with surviving offspring but did result in an increased frequency of totally resorbed litters. Among fetuses treated with corticosterone there was a dose related increase in hemorrhagic pigmentation of the fetal sac. Damage to the fetal sac by corticosteroids may be a basis for their teratogenic action.
The production of congenital malformations using tissue antisera XI. Antisera to acellular visceral yolk sac
Authors: Leung Christopher C. K. , Brent Robert L. , Koszalka Thomas R.
Published: June 2005

A method has been developed for obtaining cell‐free visceral yolk‐sac membrane using the chelating agent tetrasodium salt of ethylenediamine‐tetraacetic acid (EDTA) combined with mechanical disruption of cells. Rabbit antiserum to this acellular membrane preparation when injected ip into 8‐day pregnant rats produced malformation, growth retardation, and fetal resorption. This yolk‐sac membrane was partially solubilized with sodium deoxycholate. The resultant insoluble material was further partially solubilized by 1 M NaCl and fractionated by molecular sieve chromatography on BioGel A‐5m to yield two fractions. The insoluble material after NaCl extraction was treated with purified collagenase to obtain a soluble and insoluble fraction. Rabbit antisera to all five soluble and insoluble fractions proved to be teratogenic in rat. Immunodiffusion studies indicated that there was at least one common antigen in all of these fractions; antisera to these fractions also crossreacted with soluble rat kidney. Fluorescent‐labeled antibody localization studies revealed that the teratogenic antibodies localized in the maternal renal glomerular basement membrane and the yolk‐sac placenta. The findings that (1) the hydroxyproline‐free collagenase‐treated residue was capable of stimulating the production of teratogenic antiserum and (2) rabbit antiserum against undenatured rat‐tail collagen was not embryotoxic provide evidence to support the view that antibodies against collagen fibers are not teratogenic. The hypothesis that teratogenesis resulting from yolk‐sac dysfunction induced by heterologous antibodies was discussed.
Transplacental uptake of 127mtellurium studied by whole‐body autoradiography
Authors: Agnew William F.
Published: June 2005

Whole‐body autoradiographs and direct tissue counts demonstrated that, tellurium reached rat embryos during the period of teratogenic sensitivity for induction of hydrocephalus (gestation days 9–10). Progressively decreased concentrations occurred with increasing offspring age, but equilibration between maternal and fetal levels did not occur at any gestational stage. Autoradiographs of late fetuses revealed a prominent accumulation of tellurium by the choroid plexus and also development of the blood‐brain barrier to this metal.
Cleft palate formation: A role for pyridoxine in the closure of the secondary palate in mice
Authors: Miller Tony Jasper
Published: June 2005

Dietary pyridoxine deprivation in mice throughout pregnancy produced 20% cleft palate (CP). This frequency was significantly increased when either 4‐deoxypyridoxine or cortisone was administered during the period of palate closure. A low dose of cortisone given to pregnant mice fed a pyridoxine‐deficient diet produced a CP frequency greater than the sum of those produced by each teratogen alone. At a higher dose the interaction between cortisone and pyridoxine deficiency was additive. The effects of cortisone and pyridoxine deprivation were mitigated when pyridoxine was given during the time of palate shelf movement. Clearing arid staining for bone formation revealed general delay of ossification but no visible skeletal defects. Exencephaly, with a frequency of 0.4 %, was the only other gross defect seen after maternal pyridoxine deprivation.
Teratological experiments with ergotamine in mice, rats, and rabbits
Authors: Grauwiler J. , Schön H.
Published: June 2005

Pregnant mice, rats, and rabbits were treated orally with ergotamine during midgestation. In doses that affected maternal weight gain during treatment, ergotamine produced an increase in prenatal mortality in rats and evidence of fetal retardation in all three species. The results are discussed in connection with the vasoconstrictive action of ergotamine. A uterotonic effect may also be involved in the mechanism of action. No specific teratogenic activity was detected in any of the three species.
The teratogenicity of cadmium chloride in two stocks of Wistar rats
Authors: Barr Mason
Published: June 2005

The teratogenicity of cadmium chloride (16/μM/kg Cd++) was studied in Wistar rats from two commercial sources. Subcutaneous cadmium was not teratogenic. Intraperitoneal cadmium was highly teratogenic in both stocks when given on day 9, 10, or 11 of gestation. There were marked differences between the two stocks in fetal mortality and the incidence and types of malformations produced. Cadmium on day 9 produced an attenuation of the abdominal wall in 13–16% of the term fetuses. In one stock of rats, cadmium on day 10 produced reduction deformities of one forelimb similar to the previously reported acetazolamide syndrome in rats.
Ethylenethiourea: Teratogenicity study in rats and rabbits
Authors: Khera K. S.
Published: June 2005

Ethylenethiourea (ETU) was administered orally in single daily doses of 0, 5, 10, 20, 40, or 80 mg/kg to nulliparous rats and rabbits. In rats treatment was made from 21–42 days before conception to pregnancy day 15, and on days 6–15 or 7–20 of pregnancy, and in rabbits on days 7–20 of pregnancy. ETU induced meningoencephalocele, meningorrhagia, meningorrhea, hydrocephalus, obliterated neural canal, abnormal pelvic limb posture with equinovarus, and short or kinky tail after 10 mg/kg or more in all rat experiments. Fetal survival was not affected at any dose, whereas fetal growth was retarded at 40 and 80 mg/kg. The incidence of most of the deformities was dose dependent. Results from the rabbit study suggested an increased incidence of resorption sites and decreased brain weight in the group given 80 mg/kg, but no malformations were seen.