Reinforcing the vascular disruption theory of the genesis of Poland's syndrome: a rare association of diaphragmatic eventration in a preterm infant with severe musculoskeletal defects.

A preterm female infant was admitted at birth with respiratory distress. On examination, she had an asymmetric right chest wall and ipsilateral small hand. Air entry was reduced over the right chest. A clinical diagnosis of Poland's syndrome was made based on the hypoplasia of the right pectoral muscles, absent nipple, deformed ribs and symbrachydactyly of the ipsilateral hand. Chest X-ray suggested and ultrasound confirmed eventration of the right hemidiaphragm. 'Subclavian artery supply disruption sequence' (SASDS) theory by Bavnick and Weaver remains the most accepted pathogenic mechanism in Poland's syndrome. This case reinforces SASDS theory associated with the genesis of Poland's syndrome that relates to the pathogenicity of vascular disruption of subclavian artery, characteristics of which are unilateral pectoral defects, symbrachydactyly and eventration of the diaphragm. At 2 months, she underwent diaphragm plication. She is under review by our multidisciplinary surgical team for reconstruction of the chest deformity.

The Etiologies of Chest Wall and Breast Asymmetry and Improvement in Breast Augmentation.

Patients presenting for correction of breast and chest wall asymmetries may have undergone numerous thoracic procedures in early childhood and may have suffered profound psychosocial effects. Complex congenital syndromes as well as mild breast asymmetries should be carefully documented using objective measurements, photography, and 3-dimensional simulations when available. Shaped highly cohesive breast implants offer plastic surgeons more possibilities and precision by fine-tuning the gel distribution and specific volumes required to correct the hypoplastic elements. Long-lasting correction of asymmetry can be obtained when patients are not oversized, and care is taken to avoid visibility, palpability, and malposition problems.

Prenatal diagnosis of musculoskeletal conditions.

Ultrasonography is a safe, cost-effective tool used to prenatally detect common musculoskeletal conditions, including clubfoot, skeletal dysplasias, limb-length discrepancies, spinal abnormalities, and hand and other upper extremity deformities. With increased detection of such abnormalities, prenatal parental counseling by orthopaedic surgeons is being requested more frequently. Counseling is important for family education on prognosis and treatment options. A thorough understanding of the common musculoskeletal conditions diagnosed on prenatal ultrasonography, classification of these conditions, and the correlations of these classifications to postnatal severity allows the orthopaedic surgeon to conduct well-informed counseling sessions with families. Accurate information and counseling aids parents in understanding their child's diagnosis, assists clinicians in planning treatment algorithms, and optimizes family preparedness.

Biomechanics of foetal movement.

Foetal movements commence at seven weeks of gestation, with the foetal movement repertoire including twitches, whole body movements, stretches, isolated limb movements, breathing movements, head and neck movements, jaw movements (including yawning, sucking and swallowing) and hiccups by ten weeks of gestational age. There are two key biomechanical aspects to gross foetal movements; the first being that the foetus moves in a dynamically changing constrained physical environment in which the freedom to move becomes increasingly restricted with increasing foetal size and decreasing amniotic fluid. Therefore, the mechanical environment experienced by the foetus affects its ability to move freely. Secondly, the mechanical forces induced by foetal movements are crucial for normal skeletal development, as evidenced by a number of conditions and syndromes for which reduced or abnormal foetal movements are implicated, such as developmental dysplasia of the hip, arthrogryposis and foetal akinesia deformation sequence. This review examines both the biomechanical effects of the physical environment on foetal movements through discussion of intrauterine factors, such as space, foetal positioning and volume of amniotic fluid, and the biomechanical role of gross foetal movements in human skeletal development through investigation of the effects of abnormal movement on the bones and joints. This review also highlights computational simulations of foetal movements that attempt to determine the mechanical forces acting on the foetus as it moves. Finally, avenues for future research into foetal movement biomechanics are highlighted, which have potential impact for a diverse range of fields including foetal medicine, musculoskeletal disorders and tissue engineering.

Using zebrafish as a model system for studying the transgenerational effects of dioxin.

2,3,7,8 Tetrachlorodibenzo-p-dioxin (TCDD) has been associated with many disease states in humans. A rising concern is that exposure early in life can lead to adult toxicity and toxicity in subsequent generations. Juvenile zebrafish exposed to TCDD (50 pg/ml in water; 1 h exposure) at 3 and 7 weeks post fertilization showed toxicity only later in adulthood. We have maintained the offspring of these exposed F0 fish to determine whether we could find adverse affects in the next two generations of F1 and F2 offspring. TCDD exposure produced a significantly higher female:male ratio in all three generations. Scoliosis-like axial skeleton abnormalities, not normally observed in controls, were present in the F1 and F2 generations descended from the treated F0 founders. Egg release and fertilization success were reduced in the TCDD lineage F1 and F2 generations. This reduction in fertility in the TCDD lineage F2 generation could be attributed to alterations in the F2 males. Using zebrafish as a model allowed the simultaneous maintenance of different generations with relatively small space and costs. The zebrafish showed clear signs of transgenerational responses persisting into generations never directly exposed to TCDD.

Study for collecting background data on Wistar Hannover [Crl:WI(Han)] rats in embryo-fetal development studies--comparative data to Sprague Dawley rats.

The purpose of the present study was to collect the background data on Wistar Hannover [Crl:WI(Han)] (hereafter Wistar Han) rats in embryo-fetal development studies from the 6 safety research facilities of pharmaceutical companies and contract research organizations. In each facility, 20 or 22 female rats were dosed with vehicle solution during the organogenesis period. As a result, no abnormalities in clinical signs and necropsy findings in dams were found. Body weights and food consumption in dams were lower than those in Sprague Dawley (SD) rats. The number of corpora lutea (13.3 vs. 16.0 in SD) and implantations (11.8 vs. 14.7) were fewer, and fetal body weights (3.66 vs. 3.70) and placental weights (0.42 vs. 0.45) tended to be lower than those in SD rats. Regarding the fetal abnormalities, the incidence of several findings such as the persistent left umbilical artery (10.4% vs. 1.1%) and cervical (5.2% vs. 0.4%), full (7.4% vs. 0.9%) or short supernumerary (64.5% vs. 9.9%) and wavy ribs (6.6% vs. 0.3%) was higher than that in SD rats. Our present study showed that they maintained a sufficient number of live fetuses and the difference in the fetal sex ratio was not observed. In conclusion, Wistar Han rats were considered to be a suitable strain for embryo-fetal development toxicity study. Since the incidence of several abnormalities was higher than that in SD rats, it may be said that to accumulate background control data is important to evaluate the embryo-fetal development toxicity study using Wistar Han rats.

Prenatal effects of natural calcium supplement on Wistar rats during organogenesis period of pregnancy.

The potential of oral exposure to calcium and magnesium citrate, a natural product obtained from dolomite, to initiate teratogenesis was analyzed in Wistar rats. Animals received calcium and magnesium citrate oral doses of 250, 500 and 1000 mg/kg during the period of gestation from day 6 to 17 post conception. Maternal, embryo and fetal toxicity was evaluated. Calcium and magnesium citrate exposure did not produce maternal toxicity assessed by clinical observations, body weight gain, food intake, hematology, biochemical parameters and necropsy finding. Signs of embryo-fetal toxicity were not observed. Skeletal and visceral malformations were seen occasionally in all drug-treated and control groups. Skeletal and visceral variations were similar in control and drug-treated groups except for incomplete ossification rib. These finding was spontaneous and unrelated to the drug. In conclusion, in this study we found that the oral exposure to rats of up to 1000 mg/kg of calcium and magnesium citrate during organogenesis did not induce significant maternal and embryo-fetal toxicity. The experimentally derived NOAEL for developmental toxicity was 1000 mg/kg.

TCDD disrupts hypural skeletogenesis during medaka embryonic development.

Defective bone and cartilage development account for a large number of human birth defects annually. Normal skeletogenesis involves cartilage development in early morphogenesis through a highly coordinated and orchestrated series of events involving commitment and differentiation of mesenchymal cells to chondrocytes followed by a highly programmed process of structural maturation. Recent developmental studies with laboratory model fish demonstrate that exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) results in cartilage and skeletal abnormalities. In this study, we exposed embryonic medaka to TCDD to induce developmental modification(s) of both cartilage and bone formation. Emphasis is placed on cell-rich hyaline cartilage of the hypural plate where both chondrogenesis and osteogenesis are impaired by TCDD exposure. In this model, TCDD exposure results in a concentration-dependent impairment of mesenchymal cell recruitment, chondrocyte cell proliferation, differentiation, and progression to hypertrophy. Gene expression of ColA2, a marker of chondrocyte terminal differentiation in hypural structures, is markedly attenuated consistent with hypural dysmorphogenesis. Assessment of hypural structure using a transgenic medaka expressing mCherry under control of the osterix promoter illustrated significant attenuation in expression of the osteoblast gene marker and lack of formation of a calcified perichondral sheath surrounding hypural anlage. Overall, these studies illustrate that TCDD impacts terminal differentiation and growth of cartilage and bone in axial structures not likely derived from neural crest progenitors in medaka hypurals.

Anomalies of thoracic outlet in human fetuses: anatomical study.

BACKGROUND: Thoracic outlet syndrome (TOS) identifies the clinical condition determined by the mechanical compression and entrapment of the subclavian vessels and the brachial plexus cords within the space delineated by the scalene muscles, the clavicle, and the first rib. To date, there are no concluding explanations concerning the real causes of the appearance of TOS in children. This is the first study to investigate the existence, frequency, and type of thoracic outlet anomalies in the prenatal stage (human fetuses). METHODS: Eighty cervical dissections (40 consecutive spontaneously aborted human fetuses) were performed, and the musculoskeletal, vascular, and nervous elements that pass through the thoraco-cervico-axillary region were investigated. RESULTS: Overall, anatomical anomalies of the thoraco-cervico-axillary region were found in 60% of the 80 cervical dissections. Nine (22.5%) of the 40 fetuses had normal bilateral anatomy. In 6.3%, the scalene hiatus had an oval shape due to the common costal insertion of the anterior and middle scalene muscles. Fibromuscular bands were found in 15% of the fetuses. Hypertrophy of the anterior scalene muscle was seen in 12.5% of the dissections. In 28.7% of the cervical dissections, hypertrophy of the C7 transversal process was noted, bilateral in seven cases. There was one case of a "C-shaped" clavicle anomaly. The absence of the internal mammary artery was noted in one case. CONCLUSION: This study shows that the presence of TOS anomalies in fetuses is not a rare occurrence, emphasizing a pathological cervical background which can be harmful in situations of cervical trauma or inflammatory processes. Having knowledge of the types of anomalies which can lead to TOS is important for performing a complete surgical correction and avoiding the high failure rate of recurrent TOS.

An anatomical study on the three-headed biceps brachii in human foetuses, and clinical relevance.

The biceps brachii (BB) is as one of the most variable muscles in the human body in terms of number and morphology of its heads. The most frequent variation is the presence of a third head, which has been reported by several authors in different populations. Our aim was to find the occurrence of the supernumerary head of BB in Turkish foetuses. Out of the 24 upper limbs of the foetuses, two (8.33%) arms were found to have a three-headed BB. The variations were present unilaterally in the right arm of one male foetus and one female foetus. In one of the cases, the third head of BB originated from the anteromedial aspect of the humerus just distal to the insertion of the coracobrachilais, medial to the brachialis, and in the other the third head was a thin muscle bundle, which arose on the lateral side of the insertion of coracobrachialis and over the origin of the brachialis. Both of them were extended distally and joined the common tendon. The occasional presence of the three-headed BB in the foetuses observed in the present study was similar to those of adults reported in previous studies. In conclusion, these variations are not rare and are interesting not only to anatomists but also to orthopaedic surgeons, plastic surgeons, traumatologists, physiotherapists, doctors dealing with sports medicine, and radiologists.

p53 coordinates cranial neural crest cell growth and epithelial-mesenchymal transition/delamination processes.

Neural crest development involves epithelial-mesenchymal transition (EMT), during which epithelial cells are converted into individual migratory cells. Notably, the same signaling pathways regulate EMT function during both development and tumor metastasis. p53 plays multiple roles in the prevention of tumor development; however, its precise roles during embryogenesis are less clear. We have investigated the role of p53 in early cranial neural crest (CNC) development in chick and mouse embryos. In the mouse, p53 knockout embryos displayed broad craniofacial defects in skeletal, neuronal and muscle tissues. In the chick, p53 is expressed in CNC progenitors and its expression decreases with their delamination from the neural tube. Stabilization of p53 protein using a pharmacological inhibitor of its negative regulator, MDM2, resulted in reduced SNAIL2 (SLUG) and ETS1 expression, fewer migrating CNC cells and in craniofacial defects. By contrast, electroporation of a dominant-negative p53 construct increased PAX7(+) SOX9(+) CNC progenitors and EMT/delamination of CNC from the neural tube, although the migration of these cells to the periphery was impaired. Investigating the underlying molecular mechanisms revealed that p53 coordinates CNC cell growth and EMT/delamination processes by affecting cell cycle gene expression and proliferation at discrete developmental stages; disruption of these processes can lead to craniofacial defects.

Early prenatal diagnosis of skeletal anomalies.

OBJECTIVE: To review experience of early prenatal diagnosis of skeletal dysplasias, and to explore diagnostic accuracy and improve management. METHODS: A retrospective review of fetal medicine unit (FMU) records was performed to identify cases where a skeletal dysplasia was suspected by 14 weeks' gestation. A literature review was undertaken to ascertain cases with a diagnosis of a skeletal dysplasia in the late first or early second trimester. RESULTS: Fifteen cases were identified from review of FMU records, including ten different dysplasias with a variety of inheritance patterns. Accurate prenatal diagnosis was made only in cases with a positive family history, and in one case each of thanatophoric dysplasia and Roberts syndrome. Review of the literature identified further cases. Increased nuchal translucency was reported in other cases subsequently diagnosed as having a skeletal dysplasia. In early pregnancy, common presenting features included short femora, abnormal skull shape and mineralisation, profile or chest. CONCLUSION: Increasing use of first-trimester combined screening for Down's syndrome, with or without detailed anomaly scanning, will result in early detection of more skeletal dysplasias. Parents must be made aware that detailed postnatal pathological and radiological examination is usually required for accurate diagnosis and prediction of recurrence risks.

Perinatal toxicity of cyfluthrin in mice: developmental and behavioral effects.

The present study was undertaken to evaluate the teratogenic and behavioral effects of perinatal exposure to cyfluthrin (Synthetic Pyrethroid) on mice offspring. Humans are exposed to this compound as it is widely used in various household insecticide formulations and in public health programmes. Pregnant females were exposed to 16 mg/kg (low dose) and 32 mg/kg (high dose) body weight cyfluthrin daily by oral intubation from gestation day 14 through parturition and lactation up to weaning. On 18th day of gestation, 50% females were euthanized for teratological studies and the remaining were allowed to deliver their pups normally. The fetuses were weighed and observed for gross external malformations and routine teratological examination was done. The neonates were observed for neuromotor reflexes (surface righting, tail hang reflex and pivoting) from day 1 up to day 7 after birth. Movement and exploratory behavior of weanlings were observed using 'open-field' and 'hole-board.' The fetuses did not show any external malformation. Skeletal aberrations observed included poor ossification of the skull and phalanges and short ribs. Surface righting and pivoting were significantly affected by the high dose. Both doses produced significant changes in the locomotion, exploration, and rearing frequencies in the open-field. The study indicates that cyfluthrin when administered at the above-mentioned doses did not elicit significant teratogenicity but both the doses caused significant difference in behavioral activities.

Transgenic over-expression of growth differentiation factor 11 propeptide in skeleton results in transformation of the seventh cervical vertebra into a thoracic vertebra.

Growth differentiation factor 11 (GDF11) is one of the significant genes that control skeletal formation. Knockout of GDF11 function causes abnormal patterning of the anterior/posterior axial skeleton. The mRNA of GDF11 is initially translated to a precursor protein that undergoes a proteolytic cleavage to generate the C-terminal peptide or mature GDF11, and the N-terminal peptide named GDF11 propeptide. The propeptide can antagonize GDF11 activity in vitro. To investigate the effects of GDF11 propeptide on GDF11 function in vivo, we generated transgenic mice that over-express the propeptide cDNA in skeletal tissue. The transgenic mice showed formation of extra ribs on the seventh cervical vertebra (C7) as a result of transformation of the C7 vertebra into a thoracic vertebra. The GDF11 propeptide transgene mRNA was detected in tail tissue in embryos and was highly expressed in tail and calvaria bones after birth. A high frequency of C7 rib formation was noticed in the transgenic mouse line with a high level of transgene expression. The anterior boundaries of Hoxa-4 and Hoxa-5 mRNA in situ expressions showed cranial shifts from their normal prevertebra locations in transgenic embryos. These results demonstrated significant effects of GDF11 propeptide transgene on vertebral formation, which are likely occurring through depressing GDF11 function and altered locations of Hoxa-4 and Hoxa-5 expression.

Comparative toxicities of aluminum and zinc from sacrificial anodes or from sulfate salt in sea urchin embryos and sperm.

The toxicity of aluminum or zinc from either sacrificial anodes (SA) or their sulfate salts (SS) was evaluated in sea urchin (Paracentrotus lividus) embryos or sperm exposed to Al(III) or Zn(II) (SA or SS, 0.1-10 microM), scoring developmental defects (DDs), fertilization rate (FR), and mitotic abnormalities. A significant DD increase was observed in SS, but not SA Al(III)- and Zn(II)-exposed embryos vs. controls. Both Al(III) and Zn(II), up to 10 microM, from SA and SS, inhibited mitotic activity and induced mitotic aberrations in exposed embryos. SA-Al(III)-exposed sperm displayed a significant FR increase, unlike Al(III) sulfate overlapping with controls. Both SA-Zn(II) and Zn(II) sulfate sperm exposure resulted in a significant FR increase. The offspring of SA-Al(III)-exposed sperm displayed a significant DD decrease, unlike Al(III) sulfate exposure. Zinc sulfate sperm exposure resulted in a significant increase in offspring DDs, whereas SA-Zn(II) sperm exposure decreased DDs. Together, exposures to SA-dissolved Al(III) or Zn(II) resulted in lesser, if any toxicity, up to hormesis, compared to SS. Studies of metal speciation should elucidate the present results.

Prenatal sonographic diagnosis of skeletal dysplasias.

OBJECTIVE: To assess the types and numbers of cases, gestational age at specific prenatal diagnosis and diagnostic accuracy of the diagnosis of skeletal dysplasias in a prenatal population from a single tertiary center. METHODS: This was a retrospective database review of type, prenatal and definitive postnatal diagnoses and gestational age at specific prenatal diagnosis of all cases of skeletal dysplasias from a mixed referral and screening population between 1985 and 2007. Prenatal diagnoses were grouped into 'correct ultrasound diagnosis' (complete concordance with postnatal pediatric or pathological findings) or 'partially correct ultrasound diagnosis' (skeletal dysplasias found postnatally to be a different one from that diagnosed prenatally). RESULTS: We included 178 fetuses in this study, of which 176 had a prenatal ultrasound diagnosis of 'skeletal dysplasia'. In 160 cases the prenatal diagnosis of a skeletal dysplasia was confirmed; two cases with skeletal dysplasias identified postnatally had not been diagnosed prenatally, giving 162 fetuses with skeletal dysplasias in total. There were 23 different classifiable types of skeletal dysplasia. The specific diagnoses based on prenatal ultrasound examination alone were correct in 110/162 (67.9%) cases and partially correct in 50/162 (30.9%) cases, (160/162 overall, 98.8%). In 16 cases, skeletal dysplasia was diagnosed prenatally, but was not confirmed postnatally (n = 12 false positives) or the case was lost to follow-up (n = 4). The following skeletal dysplasias were recorded: thanatophoric dysplasia (35 diagnosed correctly prenatally of 40 overall), osteogenesis imperfecta (lethal and non-lethal, 31/35), short-rib dysplasias (5/10), chondroectodermal dysplasia Ellis-van Creveld (4/9), achondroplasia (7/9), achondrogenesis (7/8), campomelic dysplasia (6/8), asphyxiating thoracic dysplasia Jeune (3/7), hypochondrogenesis (1/6), diastrophic dysplasia (2/5), chondrodysplasia punctata (2/2), hypophosphatasia (0/2) as well as a further 7/21 cases with rare or unclassifiable skeletal dysplasias. CONCLUSION: Prenatal diagnosis of skeletal dysplasias can present a considerable diagnostic challenge. However, a meticulous sonographic examination yields high overall detection. In the two most common disorders, thanatophoric dysplasia and osteogenesis imperfecta (25% and 22% of all cases, respectively), typical sonomorphology accounts for the high rates of completely correct prenatal diagnosis (88% and 89%, respectively) at the first diagnostic examination.

The mutation ROR2W749X, linked to human BDB, is a recessive mutation in the mouse, causing brachydactyly, mediating patterning of joints and modeling recessive Robinow syndrome.

Mutations in ROR2 result in a spectrum of genetic disorders in humans that are classified, depending on the nature of the mutation and the clinical phenotype, as either autosomal dominant brachydactyly type B (BDB, MIM 113000) or recessive Robinow syndrome (RRS, MIM 268310). In an attempt to model BDB in mice, the mutation W749X was engineered into the mouse Ror2 gene. In contrast to the human situation, mice heterozygous for Ror2(W749FLAG) are normal and do not develop brachydactyly, whereas homozygous mice exhibit features resembling RRS. Furthermore, both Ror2(W749FLAG/W749FLAG) and a previously engineered mutant, Ror2(TMlacZ/TMlacZ), lack the P2/P3 joint. Absence of Gdf5 expression at the corresponding interzone suggests that the defect is in specification of the joint. As this phenotype is absent in mice lacking the entire Ror2 gene, it appears that specification of the P2/P3 joint is affected by ROR2 activity. Finally, Ror2(W749FLAG/W749FLAG) mice survive to adulthood and exhibit phenotypes (altered body composition, reduced male fertility) not observed in Ror2 knockout mice, presumably due to the perinatal lethality of the latter. Therefore, Ror2(W749FLAG/W749FLAG) mice represent a postnatal model for RRS, provide insight into the mechanism of joint specification, and uncover novel roles of Ror2 in the mouse.

Differential regulation of imprinting in the murine embryo and placenta by the Dlk1-Dio3 imprinting control region.

Genomic imprinting is an epigenetic mechanism controlling parental-origin-specific gene expression. Perturbing the parental origin of the distal portion of mouse chromosome 12 causes alterations in the dosage of imprinted genes resulting in embryonic lethality and developmental abnormalities of both embryo and placenta. A 1 Mb imprinted domain identified on distal chromosome 12 contains three paternally expressed protein-coding genes and multiple non-coding RNA genes, including snoRNAs and microRNAs, expressed from the maternally inherited chromosome. An intergenic, parental-origin-specific differentially methylated region, the IG-DMR, which is unmethylated on the maternally inherited chromosome, is necessary for the repression of the paternally expressed protein-coding genes and for activation of the maternally expressed non-coding RNAs: its absence causes the maternal chromosome to behave like the paternally inherited one. Here, we characterise the developmental consequences of this epigenotype switch and compare these with phenotypes associated with paternal uniparental disomy of mouse chromosome 12. The results show that the embryonic defects described for uniparental disomy embryos can be attributed to this one cluster of imprinted genes on distal chromosome 12 and that these defects alone, and not the mutant placenta, can cause prenatal lethality. In the placenta, the absence of the IG-DMR has no phenotypic consequence. Loss of repression of the protein-coding genes occurs but the non-coding RNAs are not repressed on the maternally inherited chromosome. This indicates that the mechanism of action of the IG-DMR is different in the embryo and the placenta and suggests that the epigenetic control of imprinting differs in these two lineages.

Anomalous costochondral cartilage in fetal anencephaly.

Anencephaly is a human fetal malformation with absence of brain and calvarium superior to the orbits. The consequent absence of hypothalamus provides a unique model for studying human development, and therefore skeletal growth, in the absence of hypothalamic hormones and their regulatory functions. To assess the influence of hypothalamic insufficiency on cartilage development, we studied costochondral cartilage sections from eight anencephalic fetuses (18-22 weeks old) and seven controls (16-22 weeks old) with pathologies not directly related to skeletal growth. We found a previously undescribed anomalous organization of the cartilage in the anencephalic. The proliferative chondrocytes showed a disordered appearance with an increased proliferative zonal length (156 +/- 28 microm in anencephalic fetuses vs. 103 +/- 14 microm in controls, p = 0.006) and a concomitant decrease in the maturing portion, where cells form ordered isogenic groups (58 +/- 13 microm in anencephalic fetuses vs. 93 +/- 19 microm in controls, p = 0.003). In addition, cell density was significantly decreased in the proliferating and maturing zones in the anencephalic cases (84 +/- 21 vs. 130 +/- 21 cells/40 microm(2) in proliferating zone; 53 +/- 8 vs. 94 +/- 8 in maturing portion, p < 0.005). These alterations in the developing cartilage of the anencephalic may contribute to the observed growth retardation in these fetuses and reflect modifications in pituitary hormones and growth factors resulting from reduction in hypothalamopituitary function.

[Study of the radioprotective effects of TMG on teratogenic malformations in irradiated mice].

ICR mice fetuses in the organogenesis stage were used to clarify experimentally the mechanism of the protective effect of vitamin E derivant (TMG: 2-(alpha-D-Glucopyranosyl) methyl-2, -5, -7, -8-Teramethylchorman-6-working woman) on the effects of radiation. The authors paid careful attention to radiation, and the radioprotective effects of TMG on the induction of malformations was examined. Radiation is an important consideration because of its widespread use in the areas of medicine, nuclear energy, and industry. Malformations induced by radiation at the organogenesis stage, skeletal malformations, and the effects at the cellular level of embryos were examined in this research. Further, the mechanism of the protection effect of TMG against radiation-induced malformations was analyzed and observed experimentally. Thus, this study was done to provide fundamental data on the radioprotective agent TMG. It was clear that TMG exerted radioprotective effects against embryonic death and the rate of teratogenesis when administered before exposure. Such effects were also exerted against skeletal malformations and fetal body weight. In summary, radioprotective effects were observed at the whole-body level as well as at the cellular level.