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Human embryology is a core subject for medicine and current research. While animal models of development now have significant online resources available, the vast majority of human embryonic material is locked up in historic collections. When accessed today, these collections are still contributing to our understanding of human development. This paper describes two online resources for studying human development that are unlocking these invaluable collections and providing related human developmental resources. The first of these is the online Embryology website (http://tiny.cc/Embryo) that links the human developmental timeline to historic and current research findings. Secondly is the Digital Embryology Consortium (https://human-embryology.org), an international research partnership to digitise, preserve, and make the major embryology histological collections available for researchers. By making this histological material more widely available to researchers with new methods of analysis, a better understanding of human development can be reached. This also opens the opportunity for new 3D reconstruction and virtual reality representation of these embryos., (© 2019 S. Karger AG, Basel.)

The function of normal and defective candidate genes for human genetic diseases, which are rapidly being identified in large numbers by human geneticists and the biomedical community at large, will be best studied in relevant and predictive model organisms that allow high-speed verification, analysis of underlying developmental, cellular and molecular mechanisms, and establishment of disease models to test therapeutic options. We describe and discuss the pros and cons of the frog Xenopus, which has been extensively used to uncover developmental mechanisms in the past, but which is being underutilized as a biomedical model. We argue that Xenopus complements the more commonly used mouse and zebrafish as a time- and cost-efficient animal model to study human disease alleles and mechanisms., (© 2018 S. Karger AG, Basel.)

Thyroid dysgenesis (TD) is the most prevalent form of congenital hypothyroidism. Ttf-1, Ttf-2, Pax8 and the Tshr are expressed at early stages of thyroid development and are implicated in thyroid ontogeny. Mutations in these genes have been found in some cases of TD. The prevalence of familial forms of TD is significantly higher than expected if the disease was only sporadic, allowing to postulate a genetic basis of the disease. Linkage analysis and mutational screening of the four above-mentioned genes in familial forms of TD showed their exclusion as contributors to the disease in some families, implicating genetic heterogeneity and involving other genetic mechanisms. Strategies to uncover new genes involved in TD are therefore needed. We underscore differences in the temporal expression patterns during the human thyroid development with those in animal models. Further, the extrathyroid expression of these genes during human development enables to define the gene-specific malformations that may be present in patients bearing mutations. The data gathered on molecular thyroid development enable precise genetic counselling of affected families. By increasing our knowledge of thyroid development, we hope to uncover new perspectives of genetic screening and eventually of early in utero treatment., (2004 S. Karger AG, Basel.)

A rare case of multiple urological anomalies is presented. The chief complaint of the patient, a 12-year-old girl, was urinary incontinence. Radiologic and endoscopic examinations revealed that the patient had a normal left kidney and ureter, a left ectopic blind-ending ureter that opened near the neck of the bladder, and right complete double ureters with an ectopic orifice that opened on the left of the external urethral meatus. This orifice was responsible for her urinary incontinence. Right ureteroneocystostomy was performed and the incontinence was cured. An attempt was made to explain the embryological origin of the anomalies observed in this case. We postulated that during development, on the left, there were three ureteral buds on the mesonephric duct. The first bud was at the normal position and drained the left kidney in a normal manner. The second bud was cranial from the normal position on the mesonephric duct and was associated with growth in an abnormal direction. This bud made contact with the upper portion of the right metanephric mass. The last bud grew between the two aforementioned buds. This bud was not draped by the metanephric mass and became the blind-ending ureter. On the right, one ureteral bud was located on the mesonephric duct and it made contact with a metanephric mass that became the right kidney. The upper part of the right kidney was drained by the ureter that had originally been located on the left mesonephric duct. This condition should be termed crossed ureteral ectopia rather than crossed renal ectopia, since the ureter was the structure that crossed.

Despite improvements in prenatal care, the incidence of congenital malformations in diabetic pregnancies is still 3-4 times higher than in normal pregnancies. These defects could be attributed to alterations of intrauterine environment due to disorder of the maternal metabolism. If this were true, the quality of food could play a role in diabetes-induced embryotoxicity. To check this hypothesis, female CD rats were made diabetic by injecting intravenously 50 mg/kg of streptozotocin 2 weeks before mating. From the first day of pregnancy they were divided into three groups and maintained on the following diets: (1) standard diet (Italiana Mangimi); (2) purified high protein diet (protein 55%, carbohydrates 25.5%, fat 7.5%, fiber 4.5%, ash 7.5%); (3) purified normoprotein diet (protein 19%, carbohydrates 62.5%, fat 7.5%, fiber 4%, ash 7%). Nondiabetic pregnant females fed with standard diet served as negative control. No significant differences were observed in blood glucose levels among the groups (range 410-500 mg/dl). The group fed on normoprotein diet showed at term of pregnancy: (1) higher rate of resorptions; (2) lower fetal weight; (3) higher frequency of major malformations than the groups fed standard and hyperproteic diets. Although we are not able at this time to discriminate between a protective effect of a diet with a high protein content and a disruptive effect of a diet containing high quantity of carbohydrates, the results of this trial support the hypothesis of a fuel-mediated teratogenesis in diabetic pregnancy.

A case of unilateral conductive deafness since birth is described. At exploration of the middle ear, the facial nerve was found to have an anomalous course across the oval window region, the stapedial crura ending on the uncovered facial nerve. This case is believed to represent the 9th case to be recorded. This anomaly may be due to failure of union between the branchial part and otic capsule part of the stapes, in combination with a defective development of the laterohyale resulting in a partially absent facial canal.

Six new cases of the III-IV pharyngeal pouch syndrome were encountered at autopsy among 897 consecutive pediatric autoposies. All occurred in patients with conotruncal cardiac anomalies. The anatomic characteristics of the heart defect suggest a possible mechanism for the pathogenesis of this developmental anomaly. It is postulated that premature involution of the thyroidea ima artery, which is the principal embryonic blood source to the 3rd and 4th pharyngeal pouches and the ultimobranchial body, may be the critical event in the embryogenesis of the syndrome. Hemodynamic alterations in the course of anomalous morphogenesis of conotruncal anomalies may favor premature involution of certain vessels including the left 4th aortic arch and the thyroidea ima. Deficiencies of thymus, parathyroid glands and ultimobranchial tissue ("C" cells) may be the consequence of vascular deprivation during embryogenesis. These cases are discussed with regard to the proposed mechanism of pathogenesis and the influence of varying quantities of thymus upon peripheral lymphoid tissue. Both embryologic and clinical data support the possibility of a deficiency of ultimobranchial tissue. The range of minor and inconstant anomalies seen in patients with this syndrome is presented.

The results of two French collaborative studies are reported with respect to chromosomal and biochemical analyses following the ultrasonographic detection of a fetal anomaly. Overall, chromosomal anomalies were observed in 14.8%, ranging from 8.6% in isolated single malformations to 40.5% in multiple fetal malformations associated with intrauterine growth retardation. Acetylcholinesterase (AChE) electrophoresis was performed on the amniotic fluid of 64 cases of ultrasonographically diagnosed isolated hydrocephalus. 8 cases of previously unsuspected open neural tube defects were diagnosed by AChE. Digestive microvillar enzyme assays were useful in the precise diagnosis of suspected gastrointestinal anomaly. The correlation of the results of ultrasonography and chromosomal and biochemical analyses is the basis for the diagnosis and the prognosis of pregnancy.