bluuebunny/crossref_metadata_2025 huggingface dataset:
Teratogenicity of ethylenethiourea and thyroid function in the rat
Authors: Lu M.‐H. , Staples R. E.
Published: June 2005

Ethylenethiourea (ETU) was given by gavage at a dose of 40 mg/kg/day from Days 7 through 15 of gestation to hypothyroid and euthyroid rats, and to rats given exogenous thyroxine, to determine whether ETU teratogenicity occurs through alteration of maternal thyroid function. At sacrifice on Day 20 of gestation 84‐100% of the fetuses in all groups given ETU were malformed regardless of the thyroid status of the dams. Ten percent of the fetuses of dams thyroparathyroidectomized at 75 days of age that were not given ETU were malformed; no malformations were noted among the fetuses of the other groups not given ETU. Hence, ETU was found to induce teratogenicity in rats but not through alteration of maternal thyroid status. In addition, it was determined that ETU lowered serum thyroxine concentration, that hypothyroidism itself increased the background level of malformations in the rat, and that hypothyroidism qualitatively and quantitatively increased the incidence of specific malformations after ETU administration.
Ultrastructural observations on FUdR‐induced cell death and subsequent elimination of cell debris
Authors: Langman Jan , Cardell Emma Lou
Published: June 2005

Twelve‐day mouse embryos were treated with fluorodeoxyuri‐dine (FUdR) and sacrificed at various time intervals after treatment. The neu‐roepithelial cells were then examined to determine by electron microscopy the primary site of action of the drug. About two hours after treatment mitotic activity ceased and a number of cells were found with a normal interphase nucleus, but with a cytoplasm in which the ribosomes had lost their normal poly‐somal configuration and were dispersed as single ribosomes. At about the same time cells were seen with an accumulation of chromatin at the nuclear membrane and the segregation of chromatin masses within the somewhat denser karyoplasm. Concurrent with the nuclear changes was the appearance of a condensed cytosome containing monoribosomes. The condensation of the nucleus and cytoplasm was followed by fragmentation of the cell into membrane bound bodies. Since condensed cells always contained monodispersed ribosomes, it seems likely that the dispersal of the ribosomes is the first morphological sign of the action of FUdR.

Since about half of the neuroepithelial population underwent cell degeneration, the second goal of this experiment was to study the fate of the dying cells. Some fragments from condensed cells were found within apparently normal neuroepithelial cells, indicating phagocytosis. In addition macrophages were seen containing phagosomes from fragmented cells. Most of the fragments, however, remained free and were not immediately phagocytosed. These un‐phagocytosed fragments lysed and became ghosts, thereby giving the neu‐roepithelium a vacuolated appearance. Hence, cellular debris was eliminated partially by neuroepithelial cells, partially by macrophages and to a great extent by lysis.
Multifactorial contributions to the etiology of spontaneous hemorrhagic necrosis of the central nervous system of fetal hamsters
Authors: Keeler Richard F. , Young Stuart
Published: June 2005

Experiments were performed to learn whether males or females of various hamster strains or crosses played a role in the etiology of spontaneous hemorrhagic necrosis (SHN) disease. Disease incidence in fetal hamsters was highly variable in 1,185 observed litters of one hamster strain over a 1‐year period. There was no evidence of Gaussian distribution of incidence among the 177 affected litters to suggest that SHN is a directly transmissible, highly contagious disease. The 177 litters were sired by 39 of 51 males used to breed the 1,185 females; each male sired a total of from 8 to 48 litters. In sequential litter progeny of males that did sire SHN litters, affected litters did not occur at any one period or with any consistent pattern within the males' breeding use. However, direct contact among bred females influenced incidence. Various hamster strains and crosses were examined for susceptibility to SHN disease. In counterpart breedings offspring from the Simonsen, the Lakeview PD4, the Lakeview MHA, and the Lakeview LVG strains all developed SHN, but the Engle strain did not. Among crosses, those involving a Simonsen dam but not those involving an Engle dam were affected with the disease, regardless of the strain of male used. The fact that only certain strains or crosses were free of the disease suggests that genetic factors played an important role in susceptibility.
The induction of axial blisters in the chick embryo by trypan blue
Authors: Nadeau J. H. , Mun A. M.
Published: June 2005

The hemorrhage, blister formation, and rumplessness observed in the chick embryo following treatment with trypan blue may be due to (1) increased ventricular blood pressure or (2) to necrosis and edema in the caudal region of the embroyo by inhibititing nutrient utilization. To test the role of increased ventricular blood pressure in the induction of caudal blisters, primitive streak to 7‐somite chick embryos were cut in half, separating the upper presumptive heart region from the lower presumptive trunk and tail regions. Each half was then explanted on media containing trypan blue for 24 hours. In intact embryos treated with 0.04 mM trypan blue the frequency of blisters in theposterior region was 80.8%. The blisters usually appeared on both sides of theneural tube, below or in the region of the last few somites. In transected embryos treated with trypan blue, the frequency of blisters in the anterior halves which had beating hearts was 2.6%. Howeverm the frequency of blisters in the posterior halves which were not connected to beating hearts was 47.8%. In some cases the blisters were found in posterior haves in which the rump was not well developed or present at all. Thus, we may conclude that: (1) direct connection beteen the heart and the rump is not necessary for the induction of caudal blisters. (2) The presence of a well‐differentiated rump is also not necessary for blister formation. We suggest that trypan blue acts directly on organs or structures found in the caudal region of the chick embryos.
Myeloschisis in a six weeks embryo of a leukemic woman treated by busulfan
Authors: Abramovici A. , Shaklai M. , Pinkhas J.
Published: June 2005

A case of myeloschisis in a six weeks old human embryo is reported. The 39‐year‐old mother was treated by busulfan before and during the early stages of gestation for chronic lymphatic leukemia. Additional histological findings consisted in a decrease of mesenchymal elements together with a somitic disorganisation in the affected area of the embryo. In spite of the well known experience that this drug is well tolerated by leukemic pregnant women, a possible interference of busulfan with the oocyte differentiation in this elderly primipara is proposed.
Use of dose‐response relationships to discriminate between the mechanisms of cleft‐palate induction by different teratogens: An argument for discussion
Authors: Biddle F. G.
Published: June 2005

The examples of 6‐AN‐ and cortisone‐induced cleft palate in the mouse suggest that dose‐response studies can be used to discriminate whether mechanisms of action are different for different teratogens. Evidence for differences in the mechanisms of teratogenic action can be found in terms of the parameters of the response without reliance on other consequences of teratogen treatment. It is argued that the application of established biometrical models or, possibly, the development of new ones is critical to consolidate enumerative data. With practical methods, genetic variation can be sought, interpreted and put to experimental use, structure‐function studies can be made intelligible, and safety evaluation programs might begin to make sense.
Cell ploidy in molar placental disease
Authors: Poland B. J. , Baillie D. L.
Published: June 2005

Molar disease of the placenta is associated with cystic change in the villi. The cysts may be from 5–20+ mm in diameter. This disease has been described in association with triploid and diploid cell lines and with and without an accompanying embryo or fetus. It may be followed by malignant change and invasive chorio‐carcinoma. In order to investigate the association between cell ploidy, embryonic development and subsequent malignancy, a detailed study of 30 conceptuses with molar disease was made, with the accompanying maternal history and follow‐up. The cell ploidy was determined by measurement of nuclei by a cytoscan light microscope connected to a computer program as has been previously described. Diploid cell lines were not found with embryonic or fetal development. Triploid cell lines were always associated with an embryo or fetus. Triploidy is not associated with hyperplastic changes in the trophoblast. These results are presented and discussed.
Cyclopia associated with triploidy and hydatidiform mole: A case report
Authors: Deligdisch Liane , Legum Cyril , Peyser M. R. , Toaff R.
Published: June 2005

A live 22‐week‐old cyclops fetus with a 69 XYY chromosome pattern and partial hydatidiform mole of the placenta is reported. Although cyclopia and chromosomal triploidy have certain features in common they appear to be two quite distinct entities. As no other 69 XYY fetus has survived to 22 weeks gestation and no other case of cyclopia has been reported with a triploid set of chromosomes, the assumption that the two conditions occurred coincidently in this fetus will have to await the accumulation of additional case reports.
Triploidy in human abortions
Authors: Ornoy A. , Kohn G. , Zur Z. Ben , Weinstein D. , Cohen M. M.
Published: June 2005

Seven triploid embryos and fetuses, six spontaneously aborted and one resulting from pregnancy interruption are described. A wide range of malformations, from amorphous, nodular embryos, to apparently normal phenotypes were observed. The degree of hydatid degeneration in the placentae ranged from minimal to severe. In several cases large, atypical cells were present in the villous stroma. There was no apparent correlation between the degree of placental lesion and fetal malformations. It is suggested that termination of triploid pregnancies is determined more by the degree of placental damage rather than the severity and type of fetal anomalies.
The differentiation of the columella in avian embryos treated with hadacidin with some observations on other skeletal abnormalities
Authors: Jaskoll T. F. , Maderson P. F. A. , Weiner B. E.
Published: June 2005

Single doses of N‐formyl hydroxyaminoacetic acid (hadacidin) were injected into chick embryos HH stages 5–30. Embryos surviving for 8 + days total incubation time were recovered and examined for gross and microscopically observable defects. Particular attention was paid to the development of the columella. Survival was only 20%, but a high incidence of cranio‐facial and hind limb defects was observed in most age groups. While three categories of columella defect were observed, reflecting some degree of age dependency, this chondrogenic tissue is less susceptible to teratogenic action than other skeletal tissues. The types of columella defect observed are interpreted in the light of a model of cellular interactions in fenestra vestibularis differentiation presented previously. It is concluded that hadacidin produces abnormalities of skeletal differentiation by disrupting morphogenetic, rather than the initiative phases of development of particular elements.
Effect of maternally administered sodium nitrite on hepatic erythropoiesis in fetal CD‐1 mice
Authors: Globus Morton , Samuel Daisy
Published: June 2005

A commonly used food preservative, sodium nitrite, was administered to pregnant CD‐1 mice at a concentration of 0.5 mg/mouse/day. Embryotoxic and teratogenic effects on the hemopoietic tissues and skeletons of their offspring, were evaluated. Fetal mortality, resorptions, the mean number of offspring per litter, the mean weight per embryo and the incidence of skeletal malformations, were not significantly different from controls.

Hemopoietic cell suspensions, prepared from the livers of treated and control 14‐, 16‐ and 18‐day embryos, were cytocentrifuged onto microscope slides and differential counts were performed after staining with benzidine and Wright‐Giemsa stain. The results indicate that maternally administered Na nitrite, stimulates fetal hepatic erythropoiesis. This was manifested in a statistically significant increase in the percentage of polychromatophilic erythroblasts and mature erythrocytes at 14 and 16 days of gestation, respectively. The possibility that Na nitrite may induce fetal methemoglobinemia is discussed and mechanisms responsbile for the observed erythroid stimulation, are considered.
Teratogenic effects of hyperthermia in the bonnet monkey (Macaca radiata)
Authors: Hendrickx Andrew G. , Stone Gary W. , Henrickson Roy V. , Matayoshi Kunio
Published: June 2005

Seventeen timed‐mated bonnet monkeys (Macaca radiata) were exposed to hyperthermia in a forced‐draft incubator for a duration of one, three, four or eight days between 21 and 46 days of gestation. On each day of exposure the core temperature of the pregnant animal was elevated 2.4 to 5.4°C above the reference temperature recorded before heat exposure. Malformations occurred following a one‐hour daily elevation of the core temperature above the reference temperature under the following exposure conditions: 3.8°C, days 23 to 26; 3.9°C, days 24 to 27; 2.4°C, days 27, 28 and 30; and 4.1°C, day 26 of gestation. Five resorptions occurred following exposure for one, three or four days between days 24 and 29 of gestation after core temperature elevation of 3.7 to 4.4°C and three abortions occurred following exposure for four days between days 24 and 35 of gestation after core temperature elevation of 2.6 to 3.9°C. The results clearly indicate that the teratogenic sensitive period is from 23 to 30 days gestation following elevations of the core temperature from 2.4 to 4.1°C. No distinct pattern of malformations was observed although skeletal and umbilical cord malformations were the most common. Pathological changes in placental structure, expecially maternal surface infarctions and intervillous thrombi, were associated with three of the four abnormal fetuses, suggesting a relationship between pathological placental characteristics and fetal malformations in this study. The degree of core temperature elevation which resulted in malformations in the present study are similar to those applied to other mammalian species, and the specific anomalies observed in the bonnet monkey resemble those observed in other mammalian species, including man.
Light microscopic and ultrastructural observations in advanced stages of induced exencephaly and spinal bifida
Authors: Peters P. W. J. , Dormans J. A. M. A. , Geelen J. A. G.
Published: June 2005

This investigation was performed to demonstrate the morphologic basis of the elevation of fetal proteins in the amniotic fluid of fetuses with neural tube defects. Pregnant rats were treated with hypervitaminosis A to induce exencephaly or with trypan blue to produce spina bifida aperta. The malformations were studied on days 15ndash;20.

On day 15 of gestation, edema developed in the primitive nervous tissue. This was followed by the appearance of quickly expanding hemorrhages throughout the ventricular and intermediate zones. Some capillaries did not rupture but collapsed and showed degenerative changes of the endothelium, probably due to lack of blood perfusion. The ventricular layer in exencephaly and spina bifida aperta was exposed to the amniotic cavity due to non closure of the neural tube. On day 17, this superficial lining of the primitive nervous tissue was disrupted by the expanding hemorrhages and subsequent necrosis. As a result vast amounts of fetal blood and cell debris were extruded into the amniotic fluid. During days 18 to 20, the degeneration of the nervous tissue proceeded rapidly. This process showed the same features in the ventricular cells, the primitive neurons and the neurons. Initially it was characterized by condensation of the nuclear chromatin and the cytoplasm, irregular outlines and breakdown of the plasma membrane. Only part of the cell debris was phagocytozed by macrophages.

It is concluded that the leakage of fetal serum and cell debris causes the elevation of fetal protein levels in the amniotic fluid of fetuses with open neural tube defects.
Plastic casts of embryonic respiratory and cardiovascular system: A technique
Authors: Clark Edward B. , Rooney Patrick R. , Martini D. Richard , Rosenquist Glenn C.
Published: June 2005

This report describes a technique for producing plastic casts of the cardiovascular and respiratory systems of the chick embryo at Stage 36 or older. For casts of the cardiovascular system, polymerization compound is injected in the right ventricle filling the heart, venous, and arterial system. A two stage injection produced more detailed casts of the pulmonary vasculature. For respiratory system casts, the compound is injected in the trachea filling the bronchi and air sacs. Casts are prepared by tissue corrosion in 10% potassium hydroxide. This technique is an alternative to serial section reconstruction in the study of developing cardiovascular and respiratory system.
Effect of the brachypod mutation on early stages of chondrogenesis in mouse embryonic hind limbs: An ultrastructural analysis
Authors: Duke Jackie , Elmer William A.
Published: June 2005

This paper is an ultrastructural investigation of the early chondrogenic events which occur in the tibia and fibula blastemata of normal and brachypod embryos during 12‐; and 13‐days of development. Transverse sections taken within the central core of the 12‐day normal fibular blastema revealed a characteristic morphology consisting of elongated cells with long cytoplasmic filopodia separated by matrix which contained granules and fibers. In 12‐day brachypod embryos the cells within the fibular blastema portrayed an atypical morphology. The cells were more closely associated, exhibited small spiky microvilli rather than long cytoplasmic filopodia, had more extensive intercellular contacts and were deficient in matrix. The brachypod tibial blastema in embryos of the same age displayed a quasi normal appearance. More matrix was present, filopodia were apparent but shorter than normal and numerous sections of filopodial processes were observed in the intercellular spaces.

Fibular regions of 13‐day normal limbs exhibited spacing and morphology similar to 12‐day limbs, but had more matrix material. Cells in the fibular region of 13‐day brachypod limbs presented a normal morphology and arrangement, but matrix granules were still scarce and aggregation of collagen was abnormal. An explanation of how these differences may contribute to the expression of the brachypod phenotype is offered.
Some effects of continuous low‐dose congenital exposure to methylmercury on organ growth in the rat fetus
Authors: Chen Wei‐Jen , Bōdy Ralph L. , Mottet N. Karle
Published: June 2005

Congenital low‐dose exposure of rat fetuses to methylmercury produced smaller offspring without anatomical abnormalities. The present study explored the mechanisms of the smallness of fetuses. The pregnant rats were given methylmercury water (25 ppm) from day 1 of pregnancy continuously until day 20 of gestation. There was a negative correlation of fetal weight and maternal and fetal mercury burden. The whole organ DNA and protein content of the livers and kidneys in the experiments were significantly lower than the control (P < 0.05) indicating that there were fewer cells per organ in the mercury exposed fetuses. When the data were compared on a per gram of tissue basis, there was no significant difference, indicating that the number and size of the cells of each were not diminished. The incorporation of 3H‐thymidine into fetal tissue DNA was also substantially lower in the experimental group indicating decreased proliferative activity. We conclude from this study that, at least for some major organs, the decreased size in the mercury exposed fetuses is due to fewer cells in the organs due to decreased proliferative activity.
Effects of influenza, mumps, and western equine encephalitis viruses on fetal Rhesus monkeys (Macaca mulatta)
Authors: Moreland A. F. , Gaskin J. M. , Schimpff R. D. , Woodard J. C. , Olson G. A.
Published: June 2005

Pregnant Rhesus monkeys were infected via instillation of influenza, mumps and western equine encephalomyelitis viruses respectively into the amniotic sacs at approximately 90 days gestation to determine if fetal infections would occur. Virus was recovered from fetal tissues after seven days in 100% of the exposed animals. Thus, the viruses are capable of causing fetal infection.

Rhesus monkey fetuses were inoculated with influenza, mumps and WEE viruses by the direct intracerebral route at approximately 90 days gestation to determine possible teratogenicity of the viruses. Influenza virus caused no malformations or measurable fetal effects. Mumps virus resulted in significant fetal mortality. WEE virus resulted in a 100% incidence of encephalitis and hy‐drocephalus. Thus, mumps and WEE viruses are teratogens in primates and are potential teratogens of man.
Fetal mortality and malformations associated with experimental infections of Western equine encephalomyelitis vaccine virus in Rhesus monkeys (Macaca mulatta)
Authors: Moreland A. F. , Schimpff R. D. , Gaskin J. M.
Published: June 2005

Pregnant Rhesus monkeys were infected via installation of Western Equine Encephalomyelitis (WEE) vaccine virus into the amniotic sacs at 50 and 80 days gestation to determine if the resulting infections would produce fetal mortality or fetal malformations, particularly within the central nervous system.

Of those receiving virus at 50 days gestation, 13 of 18 fetuses were aborted or dead in utero at time of Caesarean section; 2 of 18 were malformed (hydrocephalus and polyarthrosis); and 3 of 18 were anatomically normal. Of those receiving virus at 80 days gestation four of eight fetuses were aborted or dead in utero at time of Caesarean section, one of eight was malformed (hydrocephalus) and three of eight were anatomically normal. Three of three controls receiving neutralized virus at each gestational age were anatomically normal. Fetal WEE vaccine virus infection significantly increased fetal mortality and resulted in a significant incidence of fetal malformations.
Cerebral embryopathy in late first trimester: Possible association with swine influenza vaccine
Authors: Sarnat Harvey B. , Rybak Gottfried , Kotagal Suresh , Blair John D.
Published: June 2005

An infant girl was born with cerebral malformations characterized by developmental arrest late in the first trimester of gestation. These features included persistent pontine flexure, cerebellum developed only around the rhombic lip, failure of migration of inferior olive, absence of basis pontis and of corticospinal and corticopontine tracts, and agenesis of olfactory bulbs. The cerebral cortex was thin and poorly laminated, and primary and secondary sulci had failed to form. The choroid plexus contained vascular malformations, hemorrhages, and infarcts. The leptomeninges contained foci of primitive mes‐enchyme. The mother had received an inoculation of swine influenza vaccine six weeks after conception, followed by a 2‐week illness. The temporal relation to the timing of the cerebral malformation suggests a teratogenic effect of the vaccine, but may have been coincidental.
Sensitivity patterns for the induction of homeotic shifts in a favorable strain of mice,
Authors: Russell Liane B.
Published: June 2005

In an effort to develop a prescreening system that is sensitive, is compatible with in‐vivo administration of presumptive teratogens, and utilizes morphological endpoints, we are studying the induction of homeotic shifts in the axial skeleton. Our earlier work had demonstrated the existence of critical periods for certain such shifts, even though the (C57BL × NB)F1 hybrid used was not entirely suitable for this purpose. Using 100 R X‐rays on successive days during the period of major organogenesis, we have now analyzed the sensitivity pattern of the BALB/c, since this strain normally straddles thresholds for the position of axial borders. Mortality, birthweight, and skeletal anomalies were analyzed, in addition to the homeotic shifts. — Day 9 1/4 postconception was clearly the most sensitive stage for the production of posterior shifts at the thoraco‐lumbar border and the lumbo‐sacral border, and for increases in the number of sternebrae and costo‐sternal junctions. Anterior shift could be induced three days later, on day 12 1/4, but this was confined to only one of the four characters, the thoraco‐lumbar border. There are a number of indications that, at given stages during the study period, BALB/c embryos correspond developmentally to chronologically somewhat earlier stages of two strains studied previously. The present results do not support the hypothesis that factors influencing the quantitative skeletal characters act by way of body size. — Since homeotic shifts can be produced by a number of mechanisms and are obvious indications that developmental interference has occurred, and since such shifts are easy to score and convenient to analyze quantitatively, our identification of a highly suitable strain and of stages of maximum sensitivity in this strain should aid in making the system useful in the prescreening for chemical teratogens.
Prune perineum
Authors: Peeden Joseph Noble , Wilroy R. Sidney , Soper Richard G.
Published: June 2005

An infant, horn to unrelated parents, who had a rugated perineal mass which measured 17 cm in diameter is reported. No external genitalia or anal orifice was identified although the infant voided from a 5 mm crevice on the caudal surface of the mass. The patient died at four weeks of age. The perineal mass was made up of two separate sacs. The anterior sac resembled a urinary bladder in which two ureteral and a single vaginal orifice were identified. The posterior sac was continuous with the peritoneal cavity and contained bowel, left ovary, uterus and right kidney. The left kidney was small, polycystic and the right gonad a streak.
The extent of fetal ossification as an index of delayed development in teratogenic studies on the rat
Authors: Aliverti V. , Bonanomi L. , Giavini E. , Leone V. G. , Mariani L.
Published: June 2005

In teratogenic studies toxic effects may manifest themselves in retarded fetal development, such as a reduction in fetal weight. In searching for an additional index, the number of centers of ossification in seven skeletal districts (sternum, metacarpus, metatarsus, cervical and caudal vertebrae, anterior and posterior proximal phalanges) of rat fetuses delivered on days 19, 20 and 21 of gestation were counted and compared. Results showed uneven ossification in day‐19 and ‐20 fetuses, but sufficiently advanced, homogeneous an uniform ossification in day‐21 fetuses to provide a reliable quantitative index for evaluating retarded fetal development. It is therefore proposed that the stage of skeletal ossification in day‐21 fetuses be used in teratogenic studies in the rat to evaluate retarded fetal development.
Cerebellar malformations in prenatally X‐irradiated rats: Quantitative analysis and detailed description
Authors: Inouye Minoru
Published: June 2005

Pregnant WKAHok rats were exposed to 100 R or 200 R X‐irradiation on one of gestation days 16 through 21. Offspring were killed at 60 days of age and the cerebellum was examined. The cerebellum of animals exposed to 200 R was slightly reduced in weight but not in width. The observed reduction in the dorsoventrai length of the cerebellum was more evident when the X‐irradiation was early in gestation. The anteroposterior length of the hemispheres increased following exposure to X‐ray on days 16 through 19, and that of the vermis and paravermis decreased following treatment on days 17 through 21. Therefore, the anterior portions of hemispheres were situated anterior to the culmen in every 200 R group. Somewhat anteroposteriorly and horizontally directed lobules, as opposed to the normal transverse arrangement, were seen in the cerebellum of rats treated on day 16 or 17. Lobule contortion and fragmentation and an increased number of sublobules were striking in cases treated later. Histologically, ectopic Purkinje cells in the granule cell layer and white matter appeared following X‐irradiation on day 20 or 21, but they were not found following earlier treatment. In the cerebellum of animals exposed to 100 R the reduction in size was mild and the folial abnormalities were rare, but the number of sublobules decreased.
Affinity of intramitochondrial granules for ruthenium red accompanying induced cell death in chick embryos
Authors: Allenspach Allan L. , Rhodenbaugh Timothy C.
Published: June 2005

To test the hypothesis that ruthenium red binding of intramitochondrial granules might reflect an altered or pathological state of membranes associated with degeneration, embryos were treated with 6‐AN to induce cell death in cartilaginous skeletons of chick embryos. Cervical cartilage from normal, 6‐AN‐treated and nicotinamide‐alleviated 6‐AN embryos was examined ultrastructurally for presence of IM RR‐positive granules. Mitochondria of normal cervical chondroblasts which undergo normal phenotypic expression acquire RR‐positive granules, although few mature cells are observed in young embryos. Necrotic chondroblasts, chondroblasts in various stages of degeneration, and proliferating chondrogenic cells of 6‐AN‐treated embryos all demonstrated induced RR‐positive IM granules. Foci of degenerating chondroblasts, with mitochondria demonstrating RR granules, were observed infrequently in teratogen‐alleviated tissue. The cytological features induced by 6‐AN confirm its lethal effect and the degenerative effect on membranes presumably “unmasks” mitochondrial Ca‐affinity sites which then become RR‐positive. Cytochemical observations correspond with the biochemical and structural changes induced by 6‐AN and confirm the hypothesis that RR‐positive sites are the result of pathological changes.
Intersexes in the dog
Authors: Hinsch Gertrude W.
Published: June 2005

A litter of five salukis was presented in which all of the individuals were intersexes or hermaphrodites. Anatomical abnormalities were observed. The external genitalia resembled a combination of penile sheath and vulva positioned approximately midway between the anus and umbilicus. At birth structures resembling scrotal sacs were present on either side of the genital structure. These were not apparent in older animals. Internal anatomy consisted of two gonads in a position expected for ovaries, oviducts, uterus and cord‐like structures lateral to the uterus which extended from gonad to inside of the “scrotal sacs.” Histologically. the gonads appeared to be ovaries which contained many dysgenic follicles. Cause of the condition is unknown.
Absorption of methylmercury by the fetal guinea pig during mid to late gestation
Authors: Kelman B. J. , Steinmetz S. E. , Walter B. K. , Sasser L. B.
Published: June 2005

Pregnant guinea pigs were injected with ∼ 1 μ/kg of CH3 203HgC1 at 22, 40, 47, 59, and 66 days of gestation, and fetal tissues were obtained 24 hours later. Autologous fetal erythrocytes were labeled with 51Cr and used to label the fetal blood pool at each gestational age except 22 days so that tissue‐bound Hg could be calculated. In general, Hg absorbed by the whole fetus increased during gestation, in parallel with increasing tissue mass, while Hg found in whole placentas remained the same. Hg concentrations in the whole fetus and placenta were closely correlated, as were Hg concentrations in brain, liver, and kidney. Liver, kidney, blood, and brain contained the highest Hg concentration early in gestation. While it is difficult to interpret the potential effects of the increased Hg concentrations, particular attention should be paid to the brain, since it is considered a target tissue in MeHg toxicity.
Palate morphogenesis. I. Immunological and ultrastructural analyses of mouse palate
Authors: Kuhn Evelyn Meyer , Babiarz Bruce S. , Lessard James L. , Zimmerman Ernest F.
Published: June 2005

Midpalate was analyzed for the presence of nonmuscle contractile systems. The results indicate that increased amounts of actin and myosin are present in cells of regions 2 and 3. A localization of the contractile proteins in cellular projections directed against smooth muscle myosin and against skeletal muscle actin. Specificity of the immunofluorescence reactions was ascertained by immunoabsorption studies using purified myosin and actin. Electron microscopic observations of the mesenchymal cells in region 2 revealed 70Å microfilaments along the cell periphery and packed in fliopodia‐like projections which course between the cells. These cells, which surround a small ossification center, show no orientation, but extend up to the cranial base perichondrium and down into the shelf between the tongue side epithelium and the ossification center. The cells and projections are attached to each other by adherens and tight‐like junctions, forming a putative cohesive contractile network. Putative contractile cells in region 3 are strikingly aligned perpendicular to the oral epithelium and extend one‐third of the distance into the shelf. Projections from region 3 cells are contiguous with basement membrane material of the oral epithelium. Axonal bundles and single axons were commonly observed coursing through regions 2 and 3, often seen in close association with the mesenchymal cells. Both clear and dense‐core vesicles were found in the axons and cells of these regions. The possible role of these putative nonmuscle contractile cells in palate morphogenesis is discussed.
Maternal hormone therapy and congenital heart disease
Authors: Ferencz C. , Matanoski G. M. , Wilson P. D. , Rubin J. D. , Neill C. A. , Gutberlet R.
Published: June 2005

Exogenous female sex hormone exposure was studied in the mothers of 110 infants with conotruncal malformations of the heart, born in the years 1972–75. Cases were ascertained throughout the referral area of the Maryland State Intensive Care Neonatal Program. For each case, three normal controls were chosen from the birth popoulation: Two matched on eight characteristics related to the likelihood of hormone‐taking (race, maternal age, parity, fetal losses, gestational age, delivery mode, time of prenatal registration, private/service), and one also on the infant's sex and birthweight; the third control was chosen at random.

In personal interviews, information was obtained on the mother's general health, family history, reproductive characteristics, pregnancy health, and environmental exposures. Identification of hormonal products was aided by a display of pills and packages. Maternal recall was examined in comparison to the responses of a group of mothers of infants with hypoplastic left heart (“disease controls”). Regression analysis on time elapsed since the infant's birth revealed no difference in recall between the mothers of cases and of controls.

Multilogistic regression analysis, controlling for confounding variables and for scores constructed for reproductive, malformation, and exposure risks, showed no increase in relative risk for cases when compared with matched controls. When compared to random controls, the analysis suggested a possible increase in relative risk with increased environmental exposure scores; components of the risk score were excess smoking and alcohol intake, exposure to X‐ray, drugs, paints, insecticides, and chemicals. The possible significance of this finding needs to be further investigated.
Search for maternal factors associated with malformed human embryos: A prospective study
Authors: Matsunaga Ei , Shiota Kohei
Published: June 2005

Using data from 3,474 human embryos derived form induced abortion, various maternal factors ascertained prior to morphologic examination of the specimens were analyzed in association with the frequency of malformed embryos. The overall frequency of malformed embryos was 3.3%; polydactyly, holoprosencephaly, exencephaly with or without myeloschisis, and cleft lip accounted for 88% of the total malformations. Mothers of low parity showed an increased frequency of malformed embryos. There were nine embryos form mothers with thyroid disorders, of which one was affected with exencephaly and myeloschisis and another with holoprosencephaly and polydactyly; this finding may support the relation of maternal hyperthyroidism with anencephaly suggested by previoius case reports. The frequency of malformed embryos from mothers who drank alcohol was significantly lower than from those who did not. Several possibilities were suggested to interpret this unexpected finding. No association was verified with maternal age, irregular menstrual cycles, irradiation, contraceptive methods, maternal occupation, and a smoking habit, or with parental consanguinity. The limitation of this study is discussed in relation to both negative and positive results.
Effects of maternal diabetes on early embryogenesis: II. Hyperglycemia‐induced exencephaly
Authors: Sadler T. W.
Published: June 2005

Teratogenic effects of hyperglycemia on early stages of embryogenesis were investigated using the whole embryo culture technique. Young (0–1 and 2–3 somites) and old (4–6 somites) mouse embryos were exposed for 24 h to diabetic levels of excess glucose equal to 5× and 8× the normal blood glucose levels. A high frequency of neural tube defects (exencephaly) was observed in embryos maintained at either concentration, and this effect was dose‐ and age‐dependent. Thus, younger embryos (0–3 somites) were more frequently affected than older ones, and more embryos were affected at the higher dose than the lower one. Although malformations were observed, amounts of total protein were similar between control and treated cultures except for the youngest (0–1 somite) embryos, which had significantly lower amounts of protein than controls. Histological analysis of embryos maintained in 8× glucose for 4, 8, and 24 h after initiation of culture showed only a slight amount of pyknotic debris in the neuroepithelium and revealed no other causes for the abnormality. Inhibition of neural tube closure observed in this study is similar to that occasionally described in infants of diabetic mothers, and suggests that hyperglycemia may play a role in production of the malformation.
The Down syndrome in the fetus
Authors: Stephens Trent D. , Shepard Thomas H.
Published: June 2005

A significant number of fetuses with the Down syndrome are spontaneously lost before birth; however, very few such fetuses have been described. In the present study, 13 fetuses of 127–180 mm in crown‐rump length were examined following amniocentesis diagnosis of trisomy 21 and therapeutic abortion. Four features, i.e., simian crease, clinodactyly, septal heart defects, and decreased size, were found to be relatively common in trisomy 21 fetuses as compared to controls. Other features were found to be less useful in identification. We conclude that the presence of two of the four features noted above is suggestive of trisomy 21 in the fetus.
A study of fetal growth retardation in teratological tests: An examination of the relationship between body weight and ossification of coccygeal vertebrae in mouse and rat fetuses
Authors: Ariyuki Fumio , Higaki Koh , Yasuda Mineo
Published: June 2005

We examined the relationship between body weight and ossification of coccygeal vertebrae in normal full‐term fetuses of mice and rats to reliably evaluate fetal growth retardation in teratological tests. Correlation coefficients between body weight and number of ossified coccygeal vertebrae were positive in mice and rats. However, the coefficients were variable between groups and were not statistically significant in some groups. Averages of body weight and ossified coccygeal vertebrae were variable in the normal fetuses. However, the coefficient of variation in each group was nearly constant, and the component of variance between groups (\documentclass{article}\pagestyle{empty}\begin{document}$ \hat\sigma $\end{document}12) was small as compared with that within groups (\documentclass{article}\pagestyle{empty}\begin{document}$ \hat\sigma $\end{document}02). Therefore, the relationship between low body weight and retardation of ossification observed in teratological experiments may be evaluated by measuring relative differences of body weight and ossification between the treated group and the control group with the variance within groups (\documentclass{article}\pagestyle{empty}\begin{document}$ \hat\sigma $\end{document}0) as a scale.
An electrocardiographic study of cardiovascular problems in mirex‐fed rat fetuses
Authors: Grabowski Casimer T. , Payne Doris B.
Published: June 2005

Sperm‐positive female rats were intubated with pesticide, Mirex, in oil (5 to 10 mg/kg) on days 8½ to 15½. Controls were untreated or oil‐fed. Testing was done on day 18½. Fetuses were sequentially exposed and ECGs obtained with the fetus attached to the placenta and uterus. Counterparts of standard leads, I, II and III were used. Fetuses were weighed and examined afterwards. Swollen fetuses were rated on a scale of 1 (slight edema under chin) to 5 (3 mm edema across back). ECGs from 81 controls and 205 Mirex fetuses were obtained. They were evaluated for rate of heart beat, regularity of beat, PR intervals, and other features. One control exhibited an abnormality, a transitory period of premature atrial contractions. Mirex‐fed fetuses frequently exhibited tachycardia, closely correlated with degree of edema. The heart rate increased from 150/minute in controls to 180 in slightly swollen to 224 in swollen fetuses. Mean PR intervals increased with degree of swelling and with dose. The frequency of first degree heart‐block was also dose‐related, ranging from 20% in the 5 mg/kg group to 77% in the 10 mg/kg group. Second‐degree heart‐blocks were found in 8%, 3% showed arrhythmias, and one had atrial flutter/fibrillation. These cardiovascular problems seem primarily related to the Mirex‐induced edema and demonstrate that fetal edema is not innocuous. These data demonstrate the usefulness of fetal electrocardiography to detect functional teratology.
Nonteratogenicity of a structural analog of thalidomide in pregnant baboons (Papio cynocephalus)
Authors: Hendrickx A. G. , Helm F.‐Ch.
Published: June 2005

Teratologic evaluation of a mild tranquilizer being developed for human therapeutic use involved daily oral administration to 29 baboons (P. cynocephalus) during organogenesis according to three treatment regimens. In Phase I, 9 animals (3 groups of 3) received 2, 6, or 20 mg/kg CG 3033 per day for 28 consecutive days between 18 and 45 days gestation; in Phase II, 14 animals (7 groups of 2) were given 20 mg/kg CG 3033 for four consecutive days: 18–21, 22–25, 26–29, 30–33, 34–37, 38–41, or 42–45; and in Phase III, 6 animals (2 groups of 3) were administered 40 mg/kg daily between days 18–21 or 22–25 of gestation. No teratologic changes attributable to drug treatment were observed, and the abortion rate was within the range for controls.
The natural elimination of sporadically malformed mouse embryos
Authors: Kalter Harold
Published: June 2005

Female A/JKt mice ⩾ 250 days old had litters with significantly larger fetal resorption rates and offspring with significantly smaller frequencies of sporadic malformations [cleft lip ± palate (CLP) and open eyelid (OL)] than females < 250 days old. The OL frequency was reduced in litters with resorption as well as in those without, and thus was apparently associated with advanced maternal age per se; whereas the CLP frequency was reduced only in litters with resorption. It seems therefore that the frequency of CLP was reduced in the offspring of older females by preferential elimination and that of OL by another means, perhaps failure to express a tendency.
Congenital abnormalities and hormones during pregnancy: A clinical review
Authors: Schardein James L.
Published: June 2005

A review of the extensive literature on the subject indicates that sex hormones have been associated with a wide variety of adverse clinical conditions following usage during pregnancy. About 230 cases of female pseudohermaphroditism have been reported following use of hormones with androgenic potency, but masculinization observed with estrogens in a few females may represent only adrenal‐stimulated pseudohermaphroditism. Feminization of males, mostly by progestogens in some 45 cases, is unproven at present.

Realizing the limitations of the published studies when all present data are considered, there seems no justification for undue concern over the induction of nongenital congenital malformations through hormone use in pregnancy. The available data on the association to cardiac, limb, and CNS defects, and to several malformative syndromes, are not convincing: the effects appear to be remarkably nonspecific, the studies are contradicted by a large number of negative reports, and an increased incidence of defects with increased usage has not materialized. A possible exception are the CNS malformations associated with the use of the antifertility agent clomiphene, and careful surveillance is warranted at present.

While a reasonable interpretation from this review would be that hormones present no major teratogenic hazard, elimination of hormonal exposure whenever possible during pregnancy is suggested.
Embryotoxicity of various noise stimuli in the mouse
Authors: Nawrot P. S. , Cook R. O. , Staples R. E.
Published: June 2005

Different noise exposure paradigms were studied to determine their teratogenic and embryo‐fetotoxic potential in the CF‐1 mouse. Female mice were exposed from days 1–6 or from days 6–15 of gestation to one of three noise exposure paradigms which differed widely in level, spectral, and temporal characteristics. Paradigms for noise exposure were chosen to represent semi‐continuous exposure to extremely high‐intensity noise (jet engine noise at 126 dBA, from noon to midnight); to represent startling type noise composed of alarm bells, jet engine noise, or narrow band warning devices at 110 dBA, with pseudorandom onset and duration of each controlled by a microprocessor (exposure time of 18% over each 24 hour period); and finally to represent very high frequency noise (18–20 kHz tones, derived from a device commercially marketed for repelling rodents, with exposure from noon to midnight). On day 18 of gestation the females were sacrificed, their reproduction status determined, and the concepti were examined for toxicity and for external, visceral, and skeletal alterations. Maternal plasma corticosterone levels were measured at different periods of gestation. Significantly decreased pregnancy rate was noted in all groups exposed to noise except in the group exposed to the very high frequency noise from days 6–15 of gestation. Significant embryolethal effects occurred in the group exposed to the extremely high intensity jet noise paradigm, from days 1–6 of gestation, and significant fetolethal effects occurred in the group exposed to the very high frequency noise paradigm from days 6–15 of gestation. No significant noise‐related changes were noted in the incidence of structural alterations or in the concentration of plasma corticosterone.