Abnormal Embryogenesis Research Articles

The effects of zinc chloride during early embryonic development in zebrafish (Brachydanio rerio)

This study investigated the developmental toxicity of zinc chloride (ZnCl_{2}) in zebrafish embryos (Brachydanio rerio, Cyprinidae, Cypriniformes). Zebrafish embryos were exposed to 5 different concentrations of ZnCl_{2}, from the blastula stage, for 15 days under static renewal test conditions. As a result, the corresponding median lethal concentration (LC_{50}) value determined for ZnCl_2 exposure was 1.36 mg/L (0.65 mg/L as a lone Zn^{2+} ion). At 1.0 mg/L ZnCl_{2}, the exposed group's hatching began at 7 days instead of at 4 days, and most of the embryos died in the chorion without hatching at 11 and 12 days. Developmental deformities such as abnormal embryogenesis, low hatchability, delayed hatching, and reduction of newly hatched larvae, and a poor survival ratio (mortality ratio of 1.5 and 10 mg/L concentrations compared to control, P < 0.001), were observed during the embryo larval stage due to zinc exposure. Based on these results, we observed that critical and teratogenic effects of ZnCl_2 on embryonic development of zebrafish occurred at concentrations greater than 0.5 mg/L. Moreover, our results confirm that the zebrafish embryo teratogenesis assay can be a useful pretest for integrated biological hazard assessment of chemical agents used in industrial production and drug development technologies.

Supratentorial intraventricular solitary schwannoma. Case report and literature review

The objectives of this study were to present a case of a solitary intraventricular schwannoma with a review of the literature and to analyse the current theories of its origin. A 16-year-old male patient, without any pathological, genetic or familial history of significance, presented with symptoms of intracranial hypertension and progressive left brachiocrural paresis. The magnetic resonance image showed a bulky intraventricular space-occupying lesion emerging from the posterior horn of the right lateral ventricle, with an irregular nodular component intimately connected to the choroid plexus, and a multiloculated cystic component extending beyond the ventricle. A right parietal craniotomy was performed, revealing a multiloculated cyst with xantochromic fluid and a soft brownish red nodule. The lesion was dissected surrounding the periphery and coagulating a vascular pedicle related to the wall of the right lateral ventricle and its choroid plexus. Total excision was achieved. The pathological exam reported an intraventricular schwannoma (WHO grade 1). The patient evolved favourably, with no recurrence at 36-month follow-up. The literature describes less than 45 cases of schwannomas not associated to cranial nerves of the following locations: intramedullary, leptomeningeal and only 12 intraventricular cases. The three theories explaining the origin of this last group describe: (1) a neoplastic transformation of peripheral nerve fibres, (2) a neoplastic transformation of autonomic neural tissue located within the intraventricular choroid plexus and (3) an abnormal embryogenesis leading to a failed migration of the neural crest cells. Complete resection is the therapeutic goal for this benign pathology to avoid recurrence.

Cytoplasmic NANOG-Positive Stromal Cells Promote Human Cervical Cancer Progression

Tumor development has long been known to resemble abnormal embryogenesis. The embryonic stem cell gene NANOG, a divergent homeodomain transcription factor that is independent of leukemia inhibitory factor, has been reported to be expressed in germ cells and in several tumor types. However, the short-term expression and role of NANOG in cervical cancer remain unclear. In the present study, we demonstrate that NANOG exhibits cellular shuttling behavior and increasing stromal distribution during the progression of cervical cancer. Our molecular data using RT-PCR and restriction enzyme digestion show that NANOG is mainly transcribed from the NANOG gene in cervical cancer. In addition, IHC using confocal microscopy suggests that mesenchymal stem cells (MSCs) are one type of cytoplasmic NANOG-positive cells in cervical cancer stroma. Co-culture of cervical cancer-derived MSCs with SiHa cells showed increased proliferation characteristics in vitro and enhanced tumor growth in vivo. Our results show, for the first time to our knowledge, that MSCs are a source of cytoplasmic NANOG expression in the cervical cancer stroma and that they participate in the progression of cervical cancer both in vitro and in vivo. Our study provides evidence that NANOG is a cervical cancer progression marker and also serves as a starting point for a more extensive exploration of the cellular translocation of NANOG and the multifunctionality of the stromal microenvironment.

Aberrant Right Subclavian Artery or Arteria Lusoria: A Rare Cause of Dyspnea in Children

Aberrant right subclavian artery or arteria lusoria (AL) is the most frequent anomaly of the aortic arch, secondary to abnormal embryogenesis. It is usually asymptomatic and fortuitously discovered. It can compress neighboring structures and cause dysphagia or, more rarely, dyspnea. In symptomatic cases or in the presence of an aneurysm of the AL origin, it should be surgically treated. The case herein reported concerns a child presenting with respiratory symptomatology related to an AL that was surgically treated by right supraclavicular approach.

Genome-wide sperm deoxyribonucleic acid methylation is altered in some men with abnormal chromatin packaging or poor in vitro fertilization embryogenesis

To evaluate genome-wide DNA methylation patterns in sperm from men with abnormal sperm chromatin packaging and patients displaying abnormal embryogenesis after IVF in the absence of known female factors. Case-control study. University andrology and research laboratory. Men with abnormally high and low protamine 1/protamine 2 ratio (n = 15); patients who have undergone IVF/intracytoplasmic sperm injection resulting in abnormal embryogenesis (n = 13); and normozoospermic, fertile controls (n = 15). Genome-wide sperm DNA methylation was measured using the Illumina Infinium HumanMethylation27 BeadChip assay. Follow-up targeted methylation analysis was performed using bisulfite pyrosequencing. Methylation levels at more than 27,000 CpGs genome-wide were compared between groups. Of the 43 men analyzed, 40 displayed highly concordant methylation patterns; however, two men with abnormal protamine 1/protamine 2 and one abnormal embryogenesis patient displayed significantly altered methylation patterns across a large number of CpGs. Imprinted regions were more prone to deregulation than the genome at large. We have identified three individuals displaying broad disruption of sperm DNA methylation profiles. Although the sample set analyzed is relatively small, these results indicate that broad disruptions in sperm DNA methylation may be an important signature in some infertile men. Functional studies will be necessary to characterize the developmental consequences of such epigenetic disruption.

Bisphenol A and estrone‐induced developmental effects in early chick embryos

Endocrine disruptors, especially estrogenic substances, are thought to affect the reproduction and development of animals, including humans. We therefore assessed whether bisphenol A (BPA) or estrone (E1) had any adverse effects on chick embryogenesis. Fertilized eggs of white Leghorns were obtained within 24 h after laying. Embryos were administered 0.1, 1.0, and 10.0 mM BPA, and administered 10, 100 nM, and 1 μM E1, and incubated for 48 h at 37 ± 0.5°C and >80% relative humidity with one rotation per hour. The embryos were excised, fixed in 70% ethanol and viewed under a stereomicroscope. Their morphological abnormalities and numbers of somites were recorded. There were no significant difference in the average number of somites in embryos administered BPA and controls. Abnormal embryogenesis, however, showed dose-related increases caused by BPA and E1.

Malignant transformation of 293 cells induced by ectopic expression of human Nanog

Tumor development has long been known to resemble abnormal embryogenesis. The ESC self-renewal gene NANOG is purportedly expressed in some epithelial cancer cells and solid tumors, but a casual role in tumor development has remained unclear. In order to more comprehensively elucidate the relationship between human Nanog and tumorigenesis, the hNanog was ectopically expressed in the 293 cell line to investigate its potential for malignant transformation of cells both in vitro and in vivo. Here we provide compelling evidence that the overexpression of hNanog resulted in increased cell proliferation, anchor-independent growth in soft agar, and formation of tumors after subcutaneous injection of athymic nude mice. Pathologic analysis revealed that these tumors were poorly differentiated. In analysis of the underlying molecular mechanism, two proteins, FAK and Ezrin, were identified to be upregulated in the hNanog expressing 293 cells. Our results demonstrate that hNanog is a potent human oncogene and has the ability to induce cellular transformation of human cells.

Whole blood citrulline concentrations in newborns with non-syndromic oral clefts--a preliminary report.

The amino acid citrulline is poorly represented in food, except for the Cucurbitaceae family of fruits (watermelons, etc.) and sap from birch trees, which have both been used in the treatment of reproductive disorders for centuries. Recently, an interesting observation was published regarding citrulline as a promising candidate biomarker of abnormal embryogenesis. Our study was undertaken to investigate the involvement of newborn citrulline concentrations as potential risk factors for orofacial clefting. We performed a retrospective analysis of citrulline concentrations obtained from the results of a newborn screening program. The study group consists of 52 children with isolated cleft lip with or without cleft palate. One hundred and seven healthy children without congenital anomalies serve as controls. Whole blood citrulline levels were measured using tandem mass spectrometry. Two cut-off points of citrulline concentrations were accepted and three groups of participants were analysed: those with (1) low concentrations (< 8 micromol/L), (2) medium concentrations (8 - 16 micromol/L), and (3) high concentrations (>16 micromol/L). Low citrulline levels were significantly more frequent in patients with clefts than in children without congenital anomalies. In the control group, a high level of citrulline was observed nearly two times more often than in affected children (p=0.03). The presented findings, confirming a possible association between newborn citrulline status and the risk of an orofacial cleft, call for further studies in this area and consideration of increased consumption of foods rich in citrulline (or supplements) by women of childbearing age.

Fœtus in fœtu : à propos d’un cas

Fetus in fetu is an abnormality secondary to abnormal embryogenesis in a diamniotic, monochorionic pregnancy. It is a rare pathological condition and fewer than 100 cases have been reported in the literature. We report a neonatal case which occurred in a girl who had been hospitalized since birth because of an abdominal mass. A conventional radiograph of the abdomen revealed a right mass containing calcifications, which displaced intestinal structures to the left. Abdominal ultrasonography and CT scan revealed a vascular and heterogeneous mass that contained numerous calcifications. The diagnosis of teratoma was suspected. After surgical excision, macroscopic and pathologic examination confirmed the diagnosis of FIF.

Heat Shock Protein Cognate 70-4 and an E3 Ubiquitin Ligase, CHIP, Mediate Plastid-Destined Precursor Degradation through the Ubiquitin-26S Proteasome System inArabidopsis

Plastid-targeted proteins pass through the cytosol as unfolded precursors. If proteins accumulate in the cytosol, they can form nonspecific aggregates that cause severe cellular damage. Here, we demonstrate that high levels of plastid precursors are degraded through the ubiquitin-proteasome system (UPS) in Arabidopsis thaliana cells. The cytosolic heat shock protein cognate 70-4 (Hsc70-4) and E3 ligase carboxy terminus of Hsc70-interacting protein (CHIP) were highly induced in plastid protein import2 plants, which had a T-DNA insertion at Toc159 and showed an albino phenotype and a severe defect in protein import into chloroplasts. Hsc70-4 and CHIP together mediated plastid precursor degradation when import-defective chloroplast-targeted reporter proteins were transiently expressed in protoplasts. Hsc70-4 recognized specific sequence motifs in transit peptides and thereby led to precursor degradation through the UPS. CHIP, which interacted with Hsc70-4, functioned as an E3 ligase in the Hsc70-4-mediated protein degradation. The physiological role of Hsc70-4 was confirmed by analyzing Hsc70-4 RNA interference plants in an hsc70-1 mutant background. Plants with lower Hsc70 levels exhibited abnormal embryogenesis, resulting in defective seedlings that displayed high levels of reactive oxygen species and monoubiquitinated Lhcb4 precursors. We propose that Hsc70-4 and CHIP mediate plastid-destined precursor degradation to prevent cytosolic precursor accumulation and thereby play a critical role in embryogenesis.

Derivation of a human embryonic stem cell line from a couple with a known reciprocal translocation

OBJECTIVE: Affected embryos from patients undergoing preimplantation genetic diagnosis (PGD) have been used to derive human embryonic stem cell (hESC) lines. These can be used to investigate normal and abnormal embryogenesis. In particular, hESC lines from chromosomally abnormal embryos provide a unique method to model these rare conditions. We report the derivation and characterization of a hESC derived from a patient with a known reciprocal translocation. Chromosomal translocations are associated with several human disease states including recurrent pregnancy loss, Down's syndrome, and certain malignancies.

Congenital and Developmental Eyelid Abnormalities

Congenital and developmental eyelid abnormalities are among the most challenging problems encountered by the reconstructive surgeon. Eyelid abnormalities in children may present at birth as a result of abnormal embryogenesis (congenital) or they may occur at later stages as the child matures (developmental). These eyelid abnormalities include entropion, ectropion, ptosis, lid retraction, epicanthal folds, blepharophimosis, colobomas, cryptophthalmos, and canthal dystopias. Additional considerations include social factors regarding the child's self-awareness of their deformities, and specific anesthetic concerns related to their pediatric problems, which are often multisystem in nature. Current methods for evaluation and medical and surgical management are reviewed for each entity.

The RPN5 subunit of the 26s proteasome is essential for gametogenesis, sporophyte development, and complex assembly in Arabidopsis.

The 26S proteasome is an essential multicatalytic protease complex that degrades a wide range of intracellular proteins, especially those modified with ubiquitin. Arabidopsis thaliana and other plants use pairs of genes to encode most of the core subunits, with both of the isoforms often incorporated into the mature complex. Here, we show that the gene pair encoding the regulatory particle non-ATPase subunit (RPN5) has a unique role in proteasome function and Arabidopsis development. Homozygous rpn5a rpn5b mutants could not be generated due to a defect in male gametogenesis. While single rpn5b mutants appear wild-type, single rpn5a mutants display a host of morphogenic defects, including abnormal embryogenesis, partially deetiolated development in the dark, a severely dwarfed phenotype when grown in the light, and infertility. Proteasome complexes missing RPN5a are less stable in vitro, suggesting that some of the rpn5a defects are caused by altered complex integrity. The rpn5a phenotype could be rescued by expression of either RPN5a or RPN5b, indicating functional redundancy. However, abnormal phenotypes generated by overexpression implied that paralog-specific functions also exist. Collectively, the data point to a specific role for RPN5 in the plant 26S proteasome and suggest that its two paralogous genes in Arabidopsis have both redundant and unique roles in development.

Functional Evidence that the Self-Renewal Gene NANOG Regulates Human Tumor Development

Tumor development has long been known to resemble abnormal embryogenesis. The embryonic stem cell (ESC) self-renewal gene NANOG is purportedly expressed by some epithelial cancer cells but a causal role in tumor development has remained unclear. Here, we provide compelling evidence that cultured cancer cells, as well as xenograft- and human primary prostate cancer cells express a functional variant of NANOG. NANOG mRNA in cancer cells is derived predominantly from a retrogene locus termed NANOGP8. NANOG protein is detectable in the nucleus of cancer cells and is expressed higher in patient prostate tumors than matched benign tissues. NANOGP8 mRNA and/or NANOG protein levels are enriched in putative cancer stem/progenitor cell populations. Importantly, extensive loss-of-function analysis reveals that RNA interference-mediated NANOG knockdown inhibits tumor development, establishing a functional significance for NANOG expression in cancer cells. Nanog short hairpin RNA transduced cancer cells exhibit decreased long-term clonal and clonogenic growth, reduced proliferation and, in some cases, altered differentiation. Thus, our results demonstrate that NANOG, a cell-fate regulatory molecule known to be important for ESC self-renewal, also plays a novel role in tumor development.

Embryonal effects of t-haplotypes in mice

The effects of t-haplotypes on embryonic morphology in house mouse Mus musculus were described. Lethal mutations, t-haplotypes, in homozygotes induce abnormal embryogenesis and zygotic death at different developmental stages, which depends on the time of their action in ontogeny. Death commonly occurs in the first semester of pregnancy from the morula to the mature embryo stage (day 9-10), and the embryogenetic abnormalities and their timing were specific for each t-haplotype. Such mutations were analyzed to identify the gene products (proteins) affecting the nervous system development. The t-complex proved to contain tandem repeats coding for regulatory factors modulating the expression of specific structural genes in mouse neurons.

Embryology of oesophageal atresia

Esophageal atresia (OA) and tracheoesophageal fistula (TOF) are important human birth defects of unknown etiology. The embryogenesis of OA/TOF remains poorly understood, mirroring the lack of clarity of the mechanisms of normal tracheoesophageal development. The development of rat and mouse models of OA/TOF has allowed the parallel study of both normal and abnormal embryogenesis. Although controversies persist, the fundamental morphogenetic process appears to be a rearrangement of the proximal foregut into separate respiratory (ventral) and gastrointestinal (dorsal) tubes. This process depends on the precise temporal and spatial pattern of expression of a number of foregut patterning genes. Disturbance of this pattern disrupts foregut separation and underlies the development of tracheoesophageal malformations.

Fibropolycystic liver disease in children

Fibropolycystic liver diseases are a group of associated congenital disorders that present most often in childhood. These disorders include congenital hepatic fibrosis, biliary hamartomas, autosomal dominant polycystic liver disease, choledochal cysts and Caroli disease. We present a discussion and illustrations of the embryology, genetics, anatomy, pathology, imaging approach and key imaging features that distinguish fibropolycystic liver disease in children. The pathogenesis of these disorders is believed to be abnormal development of the embryonic ductal plates, which ultimately form the liver and biliary systems. An understanding of the abnormal embryogenesis helps to explain the characteristic imaging features of these disorders.

Newborn with multiple anomalies as a result of prenatal activation of the immune system-case report

Objectives: Beside genetic background, congenital anomalies can be also influenced by micro environmental changes as a maternal infection. Maternal immune system activation may alter the cytokine network and influence abnormal embryogenesis that leads to congenital anomalies (1).

Fetus in fetu: a case report

IntroductionFetus in fetu is a rare abnormality secondary to the abnormal embryogenesis in a diamniotic, monochorionic pregnancy. It is a rare pathological condition and fewer than 100 cases have been reported in the literature.Case presentationA 2 month old girl with an abdominal mass since birth, was referred to the Cancer Institute with a suspected diagnosis of a Wilms' tumor. Conventional radiograph of the abdomen revealed a mass containing numerous calcifications. CT scan showed a heterogeneous retroperitoneal mass containing well-defined calcified structures. The decision was made to recommend surgical exploration and the mass was successfully excised. Physical examination of the mass with review of literature confirmed the diagnosis of fetus in fetu.ConclusionAlthough it is a rare condition imaging may play an important role in the correct prospective diagnosis of fetus in fetu. Surgical excision is the recommended treatment.

Dual Inferior Vena Cava: Two Inferior Vena Cava Filters

The formation of the venous drainage system of the human body is a complex process involving structures forming and regressing in a predefined order. Interruption of any one of these steps results in the formation of a congenital anomaly. Knowledge of these anomalies can prevent us from potential serious and sometimes fatal complications. Variations from the normal anatomy of the inferior vena cava (IVC) occur in 3% of the population. The complex embryology of the IVC stems from three pairs of fetal veins: (1) posterior cardinal veins, (2) subcardinal veins, and (3) supracardinal veins. The cardinal veins constitute the main venous drainage system of the embryo. Although venous anomalies are rare, their knowledge is crucial in diagnosis and treatment. These variations should not be mistaken for pathologic finding, but should be viewed as normal findings of abnormal embryogenesis. We present a case here identifying a dual IVC, subsequently leading us to place two IVC filters.