Morphological differences between wild and hatchery-reared turbot

Reared 0-group turbot originating from Irish Sea stock were heavier at a given length than wild fish due to a greater body width and body depth. A very high incidence (96%) of abnormal lateral line canals was noted in the reared fish. It is suggested that these morphometric and morphological differences developed during the larval stage.     

The beak of the other finch: coevolution of genetic covariance structure and developmental modularity during adaptive evolution

The link between adaptation and evolutionary change remains the most central and least understood evolutionary problem. Rapid evolution and diversification of avian beaks is a textbook example of such a link, yet the mechanisms that enable beak''s precise adaptation and extensive adaptability are poorly understood. Often observed rapid evolutionary change in beaks is particularly puzzling in light of the neo-Darwinian model that necessitates coordinated changes in developmentally distinct precursors and correspondence between functional and genetic modularity, which should preclude evolutionary diversification. I show that during first 19 generations after colonization of a novel environment, house finches (Carpodacus mexicanus) express an array of distinct, but adaptively equivalent beak morphologies—a result of compensatory developmental interactions between beak length and width in accommodating microevolutionary change in beak depth. Directional selection was largely confined to the elimination of extremes formed by these developmental interactions, while long-term stabilizing selection along a single axis—beak depth—was mirrored in the structure of beak''s additive genetic covariance. These results emphasize three principal points. First, additive genetic covariance structure may represent a historical record of the most recurrent developmental and functional interactions. Second, adaptive equivalence of beak configurations shields genetic and developmental variation in individual components from depletion by natural selection. Third, compensatory developmental interactions among beak components can generate rapid reorganization of beak morphology under novel conditions and thus greatly facilitate both the evolution of precise adaptation and extensive diversification, thereby linking adaptation and adaptability in this classic example of Darwinian evolution.     

Peri‐ and postnatal rodent development of Hematide,an erythropoiesis‐stimulating agent

BACKGROUND: Aperi‐ and postnatal reproduction toxicity study was conducted in rats treated with Hematide, a synthetic PEGylated peptidic erythropoiesis stimulating agent (ESA). METHODS: Hematide, at IV doses of 0, 0.5, 3, and 15 mg/kg, was administered from implantation through lactation on gestation days (GDs) 5 and 18 and lactation day (LD) 13. RESULTS: Hematide induced pronounced polycythemia in all Hematide‐treated dams. On LDs 2 and 21, hemoglobin (Hgb) increases above control levels were 3.1, 5.2, and 5.0 g/dL and 4.1, 5.1, and 5.5 g/dL at the 0.5, 3, and 15 mg/kg/dose, respectively. There were no effects on parturition, lactation, or maternal behavior in the F0 generation female rats. A slight decrease in pup viability on postpartum days 2–4 and lower body weights and/or body weight gain for the F1 generation were associated with pronounced polycythemia and decreases in maternal body weight gain and/or food consumption at ≥3 mg/kg/dose. Hematide fetal exposure was negligible. No Hematide effect, other than on growth and survival, was noted on developmental, functional, mating, and fertility end points in the F1 generation rats, and no effect on litter or fetal parameters was observed in the F2 generation. The maternal no‐observed‐adverse‐effect level (NOAEL) for Hematide was 0.5 mg/kg, and the NOAEL for parturition and maternal behavior was 15 mg/kg. The NOAEL for F1 pup viability and growth was 0.5 mg/kg/dose. CONCLUSIONS: In conclusion, the Hematide‐associated adverse findings were attributed to exaggerated erythropoiesis (pronounced and prolonged polycythemia) resulting from administration of an ESA to pregnant animals. Birth Defects Res (Part B) 89:155–163, 2010. © 2010 Wiley‐Liss, Inc.     

Pharmaceutical Contaminants in Potable Water: Potential Concerns for Pregnant Women and Children

There has been increasing concern of late over measurable levels of pharmaceutical contaminants in drinking water. Because most data on water contaminants pertains to aquatic organisms, we wished to assess the risk of these contaminants to human health at currently reported levels. Unlike most other chemicals, there are large amounts of information for the effects of most pharmaceuticals to humans and the current model uses the clinical dose required to cause biological effects as an endpoint to assess risks for pregnant women, children, and the healthy adult population. Twenty-six drugs have been detected in water systems worldwide: 7 in drinking water, 16 in ground water and post-treatment effluent, and 3 in both. Current water treatment practices, clearly, do not always remove pharmaceutical residues. Although healthy adults are unlikely to be adversely affected at the levels of exposure reported, children were shown to have up to eightfold higher risk and may be exposed to several drugs that are contraindicated or not established for safe use in pediatric medicine. The time taken to ingest a single clinically used dose was 3.4–34,000 years. In addition, pregnant women may be exposed to several drugs that are teratogenic (range of % single doses ingested over 36 weeks was 0.0006–12.6%) and in the post-natal period to drugs that are not recommended during breastfeeding. Albeit at low levels, the exposure of pregnant women and children to contraindicated drugs through drinking water is of concern. Further research in this area should focus on integrated ecological and human health consequences of long-term, low-level exposure to pharmaceutical contaminants, particularly in pregnancy and childhood.     

Developmental stages of zebrafish (Danio rerio) embryos and toxicological studies using foldscope microscope

Zebrafish (Danio rerio), is a well‐established vertebrate animal model widely used in developmental biology and toxicological research. In the present study, foldscope is used as an innovative tool to study the developmental stages and toxicological analysis of the zebrafish embryos. Briefly, the developmental stages, such as zygote, cleavage, blastula, gastrula, segmentation, and pharyngula formation are observed and documented using simple foldscope. Toxicological parameters upon exposure to different concentration of ethanol extract of Curcuma longa and its lead compound, ar‐turmerone along with rhodamine B (bio‐coupler) on zebrafish embryos are analyzed upto 72 hr using foldscopes in live condition. The lethal endpoints, such as coagulation, lack of somite formation, non‐detachment of tail, and lack of heartbeat are clearly monitored and documented using foldscope. Bio‐evaluation of test compounds with the aid of foldscope confirms that the toxicity is directly proportional to the concentration. Our results conclude that, ethanol extract of C. longa, ar‐turmerone and rhodamine B exposed embryos remains healthy up to 96, 48, and 24 µg concentrations, respectively. Embryos exposed to higher concentrations become coagulated, however normal physiological active movement of tail lashing and heartbeat are evident in lower concentration exposed embryos. Except coagulation, no other abnormalities are observed and interestingly, the hatching ability is not delayed, when compared with the control embryos. It is confirmed that the test compounds are not highly toxic to zebrafish embryos. Hence it can be used for further analysis, especially for studying the neural‐regeneration and its neuronal development in zebrafish embryos.     

The Concept of Hormesis in Developmental Toxicology

Animal bioassay experiments are frequently conducted to assess the toxicity of chemicals on the developing fetus. Experiments are normally conducted at dosage levels that are much higher than human exposure levels to elicit the toxic reproductive effect of the chemical in a limited number of litters. Recently there has been much discussion on the fact that some chemicals may have beneficial effects at low doses and become toxic at high doses. This concept, known as chemical hormesis, has been the focus of attention in many investigations. Here, we consider the prevalence of hormesis in developmental toxicology and show that current design of developmental toxicity testing does not accommodate the study of hormesis. If it can be proved that some developmental toxicants may have stimulatory low dose effects, then design and analysis of developmental toxicity experiments need to be revised by the scientific community and the regulatory agencies. Using a thorough analysis of an experimental data set, we further demonstrate that in order to establish the possible hormetic effects of a chemical in reproduction, often a multiple replication of the experiment may be necessary to examine such effects. Using a trend test, we illustrate that while it is possible that one replicate of a developmental toxicity experiment with a known teratogen shows strong evidence of hormesis, other replicates may show no sign of beneficial effects at low doses.     

Sea urchin development: an alternative model for mechanistic understanding of neurodevelopment and neurotoxicity

Echinoderm early developmental stages might supply a good tool for toxicity testing in different fields, ranging from environment to food contamination, and in full respect of the 3Rs objectives (reduction, refinement, and replacement of animal experiments) that will eventually lead to the replacement of high vertebrate animal testing in toxicology. Sea urchin is one of the few organismic models considered by the European Agency for Alternative models. Actually, sea urchin embryonic development has been studied for over a century, and the complex nets of intercellular communications leading to the different events are well known, as well the possibility for environmental molecules and their residuals to interfere with such communications, causing developmental anomalies. In particular, the main goal of toxicologists since several years has been to establish a correlation between the cell-to-cell communications occurring during different developmental events and the signals occurring during neurogenesis, with the aim to pursue a mechanistic understanding of these processes and their deviations caused by stressors from different sources.     

Atypical Development in Plant and Soil Nematodes

Observations of atypical developmental and anatomical characteristics have been recorded for many taxa of soil nematodes. They include the unusual occurrence of extra feeding structures, aberrant configuration of features of both male and female reproductive systems, and the occurrence of intersexes assumed to be functionally female, functionally male, or non-functional. In many cases, hypotheses have been advanced regarding the genetic or developmental mechanisms and environmental stimuli that control, regulate, or facilitate abnormalities, but many are quite speculative and lack experimental verification. Further, the fitness costs or advantages, and the heritability of aberrant characters are largely unknown, except where they clearly preclude reproduction, either apomictic or amphimictic. Underlying mechanisms and ecological consequences may be difficult to study in organisms that are not readily cultured under axenic or sterile laboratory conditions, however information on developmental processes in Caenorhabditis elegans represents an important resource in which to seek homologies.     

POPULATION AND DEVELOPMENTAL VARIATION IN THE FEATHER TIP

Variation among adults reflects variation in basic developmental processes, such as cell division rate. Partitioning the variation into its developmental components would be a major step in understanding evolutionary constraints, but is far from being achieved for any character. In this paper, we examine population variation in the feather tip, a useful structure to study because the history of development is recorded in the adult form. Our goal is to document the variability, and provide a developmentally based explanation for the level of variation observed. Using feathers collected from chicks of a small warbler, we partition population variation into variation attributed to accidents of development (through a consideration of fluctuating asymmetry), and among- and within-family components. Population variation in the earliest formed part of the feather is high (the coefficient of variation is c. 30%); population variation in later formed parts of the feather is lower. The among-individual and developmental noise components are both reduced in later formed parts, but there are differences in the way the two components are associated among the feather parts. The early and later formed parts are highly integrated at the among-individual level (correlations ≈ 1.0) but not at the developmental noise level (correlations ≈ 0.5). This suggests that at least two basic developmental processes are involved in determining the length of the various feather parts. We review feather development and pattern formation models to demonstrate that at least two developmental processes are indeed involved in feather growth. We show how these processes could interact to achieve the relative invariance in the later formed parts of the feather.     

A Developmental Toxicology Assay Platform for Screening Teratogenic Liability of Pharmaceutical Compounds

Increasing need for proactive safety optimization of pharmaceutical compounds has led to generation and/or refinement of in vitro developmental toxicology assays. Our laboratory has developed three in vitro developmental toxicology assays to assess teratogenic liability of pharmaceutical compounds. These assays included a mouse molecular embryonic stem cell assay (MESCA), a dechorionated zebrafish embryo culture (ZEC) assay, and a streamlined rat whole embryo culture (rWEC) assay. Individually, the assays presented good (73–82%) predictivity. However, it remains to be determined whether combining or tiering the assays could enhance performance. Seventy‐three compounds representing a broad spectrum of pharmaceutical targets and chemistry were evaluated across the assays to generate testing strategies that optimized performance. The MESCA and ZEC assays were found to have two limitations: compound solubility and frequent misclassification of compounds with H1 receptor or GABAnergic activity. The streamlined rWEC assay was found to be a cost‐effective stand‐alone assay for supporting poorly soluble compounds and/or ones with H1 or GABAnergic activity. For all other compounds, a tiering strategy using the MESCA and ZEC assays additionally optimized throughput, cost, and minimized animal use. The tiered strategy resulted in improved performance achieving 88% overall predictivity and was comparable with 89% overall predictivity achieved with frequency analysis (final teratogenic classification made from most frequent teratogenic classification from each individual assay). Furthermore there were 21 compounds in the test set characterized as definitive or suspect human teratogens and the multiassay approach achieved 95 and 91% correct classification using the tiered or frequency screening approach, respectively     

Ontologies of developmental anatomy: their current and future roles

A central problem in current biology is elucidating the molecular networks that drive developmental change and physiological function. Such knowledge is needed partly to understand these networks, partly to be able to manipulate them, and partly to understand and help treat those human congenital abnormalities that arise as a result of mutation. Thus far, bioinformatics technology has been of limited use in this enterprise, mainly because its core focus has been on sequence technology and data archiving. For bioinformatics to be of use in this next tier of investigations, genetic and protein data need to be both archived and searchable by tissue since this is the level at which these networks operate. The resulting databases in turn require ontologies of developmental anatomy that can provide the formal infrastructure for handling gene expression, microarray and other tissue-based data. Here, the progress in making such ontologies, particularly for the developing mouse, is reported and the uses to which they are and will be put, together with the resources and tools currently available for investigating molecular networks and the genetic basis of congenital abnormalities, are considered.     

Effects of chlorpyrifos exposure on kidney Notch2-Jagged1 pathway of early prenatal embryo

Aims: To evaluate the effects of this insecticide on the embryonic development of kidney and to assess the important role of Notch2–Jagged1 pathway in this duration. Methods and results: Chlorpyrifos (CPF) 5 mg/kg/d were administrated on gestation 7.5–11.5 day by subcutaneous injection. On gestation 16.5 day, the normal embryo kidney developed through S shape duration to the original kidney, which had the nephrons and could start to secret the urine. But for the CPF‐treated mice, the embryo kidney developed much more slowly, they did not show the S shape and the nephrons. The Notch2–Jagged1 pathway should be expressed stronger in the normal embryo kidney on gestation 16.5 day, but for the CPF‐treated mice we found the obvious weak pathway staining. Conclusions : CPF broke the Notch2–Jagged1 pathway during the embryo kidney development, and the Notch2–Jagged1 pathway plays an important role in the S shape to original kidney formation duration. Birth Defects Res (Part B) 92:97–101, 2011. © 2011 Wiley‐Liss, Inc.     

A reproductive screening test of goldenseal

BACKGROUND: Goldenseal (Hydrastis canadensis L) is a multi-purpose herb (Hobbs, 1990: Pharm Hist 32:79-82) widely used for its antibiotic properties. It is traditionally contraindicated in pregnancy based on in vivo data but this contraindication has not been confirmed by conventional studies that have been peer reviewed. METHODS: Female rats were dosed by gavage using 65 times the human dose of goldenseal daily on either gestation days (GD) 1-8 or GD 8-15. Controls received an equivalent dose of ethanol. On GD 20, fetuses were weighed and examined for signs of external, internal, or skeletal malformations. Rat fetuses were also explanted on GD 10.5 and cultured with decreasing concentrations of goldenseal for 26 hr. Embryos were examined for growth retardation and malformations. RESULTS: There was no increase in pre- or post-implantation losses. There was no increase in fetal body weight in fetuses exposed to goldenseal. There was no difference in incidence of external or internal malformations. Goldenseal induced toxicity when GD10.5 embryos were cultured for 26 hr in rat serum to which extract was added. CONCLUSIONS: It is likely that poor absorption of goldenseal from the small intestine could explain the discrepancy between the in vivo and in vitro results. It is unlikely that serum concentration from oral treatment could attain the LOEL achieved in vitro. The contrasting results highlight the continuing importance of in vivo work and the necessity of pharmacokinetic data when interpreting in vitro data. The data suggest that goldenseal, at the prescribed human dose, is unlikely to be absorbed to an extent to be unsafe to use in pregnancy despite the apparent cytotoxic effects in vitro. However, these results indicate that pharmacokinetic studies are required to confirm this conclusion.     

The transport of chemicals in semen

Three mechanisms have been proposed for exposure of the conceptus to chemicals in semen: access of chemicals to the maternal circulation after absorption from the vagina, direct chemical exposure of the conceptus following transport from the vagina to the uterine cavity, and delivery to the egg and subsequent conceptus of chemical bound to the sperm cell. We review published data for each of these three mechanisms. Human seminal fluid chemical concentrations are typically similar to or lower than blood concentrations, although some antimicrobial agents achieve higher concentrations in semen than in blood. Vaginal absorption of medications has been shown to occur, although the vehicles in which these medications are delivered to the vagina may maintain contact with the vaginal epithelium to a greater extent than does semen. Assuming total absorption of a seminal dose of a chemical with a high semen:blood concentration ratio, distribution within the recipient woman would result in a blood concentration at least three orders of magnitude lower than that in the man. Direct delivery of seminal chemicals into the uterine cavity of humans has not been shown to occur, although it may occur in species such as the rat in which seminal fluid has access to the uterine cavity. Chemicals in or on human sperm cells have been demonstrated with respect to tetracycline and cocaine in vitro and aluminum, lead, and cadmium in vivo. The in vitro cocaine study offers sufficiently quantitative data with which to predict that oocyte concentrations would be five orders of magnitude lower than blood concentrations associated with cocaine abuse, assuming a maximally cocaine-bound sperm were capable of fertilizing. Thus, even using liberal assumptions about transmission of chemicals in semen or sperm, predicted exposure levels of a pregnant woman or of the conceptus are three or more orders of magnitude lower than blood concentrations in the man whose semen is the putative vehicle for chemical transport.     

FLUCTUATING ASYMMETRY DOES NOT CONSISTENTLY REFLECT SEVERE DEVELOPMENTAL DISORDERS IN HUMAN FETUSES

Developmental instability (DI), as measured by fluctuating asymmetry (FA), may reflect fitness and facilitate the expression of morphological variation. Insights in the underlying mechanisms and magnitude of DI during early development would increase our understanding of its role in evolutionary biology. We studied associations between FA and congenital abnormalities of different origins and functional systems in deceased human fetuses. Major congenital abnormalities corresponded to severe, often-lethal developmental disorders disrupting normal development from early organogenesis onward, but only moderately increased FA. Lower FA with age also supported the hypothesis that more severe abnormalities, leading to an earlier death, increased DI. Although FA related significantly to measures of fitness or health, we anticipated stronger associations because fetal health problems were detrimental. Furthermore, elevated FA occurred in only 4 of 17 disorders (left–right patterning, limb defects, and problems of bronchopulmonary and urogenital system). Fetuses experiencing major abnormalities other than these four types did not show increased FA. This suggests that the functional importance of symmetry in limbs has resulted in strong selection for symmetry and reduced its sensitivity to stress. Finally, the observed patterns suggest that specific developmental pathways have a stronger effect on DI than others do.