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A number of practical advantages have made the nematode Caenorhabditis elegans a useful model for genetic and developmental biological research. These same advantages, along with conservation of disease and stress response pathways, availability of mutant and transgenic stra ...

The founding principles of teratology/developmental toxicology state that a developmental toxicants cause dysmorphogenesis when conceptuses are exposed at a sufficient dosage during a sensitive period of development in a sensitive species. While in vitro approaches in deve ...

Teratology is the study of anatomical and physiological abnormalities, commonly known as birth defects. If an embryo is exposed to a harmful substance, or teratogen, during the critical period of development, an ensuing malformation may occur. These malformations and their associated ...

In situ hybridization (ISH) is a technique that offers the ability to detect, and assay for alterations in, the spatial distribution of gene transcripts in an organism and is thus an invaluable tool to understanding the molecular basis during various developmental processes. Changes at the m ...

Diabetic embryopathy reflects a scientific enigma—how does a seemingly rich intrauterine environment manage to disturb the development of the embryo? Which compounds in that environment may be teratogenic—and how shall we find them? How can we investigate a putative dose–response n ...

Histiotrophic nutrition is a process whereby the rodent visceral yolk sac (VYS) internalizes exogenous macromolecules, degrades them, and sends the degradation products to the embryo for use in de novo macromolecular biosynthesis. This process is important for embryonic develop ...

The direct effects of chemical exposures, environmental extremes, and nutrient quality/quantity have been very difficult to study in mammalian embryos due to their anatomical inaccessibility, paucity of tissues, and other factors such as real ethical concerns in human studies. Many ...

There is widespread interest today in the use of in vitro methods to study normal and abnormal development. The limb is attractive in this context, since much is known about pattern formation during limb development. The murine limb bud culture technique described in this chapter was developed ...

There are thousands of environmental chemicals for which there is limited toxicological information, motivating the development and application of in vitro systems to profile the biological effects of xenobiotic exposure and predict their potential developmental hazard. An a ...

In order to prevent birth defects, toxicology programs have been designed to identify toxicities that may potentially be encountered in human embryos. With appropriate toxicity data sets, acceptable exposure levels and actual safety of prescription and nonprescription drugs as w ...

Although the rabbit is used extensively in developmental toxicity testing, relatively little is known about the fundamental developmental biology of this species let alone mechanisms underlying developmental toxicity. This paucity of information about the rabbit is partly due ...

Quantification of embryonic metabolic capacity is an important tool in developmental toxicology research. Bioactivation of xenobiotics into reactive intermediates often contributes to embryo toxicity; thus, identification and quantification of these toxic metabol ...

Cytochrome P450 enzymes (CYPs) are heme thiolate proteins essential for vertebrate development and also play important roles in toxicology as well as normal metabolic function. CYP enzymes catalyze the oxidative biotransformation of many endogenous and exogenous chemicals, i ...

The electrophoretic mobility shift assay (EMSA) is a sensitive relatively straightforward methodology used to detect sequence-specific DNA–protein interactions. It is the fundamental procedure of several variants that allow qualitative and quantitative assessments of ...

Nrf2 is a transcription factor that regulates the induction of an expansive set of antioxidant proteins that act in synergy to remove reactive oxygen species (ROS). We have recently discovered that Nrf2 signaling is involved in the induction of antioxidant response in ethanol-exposed em ...

Oxidative stress can contribute significantly to the mechanisms that cause teratogenesis and embryotoxicity, but cellular antioxidant defense systems have evolved to counteract the detrimental consequences of oxidative insult. Numerous antioxidant systems exist in de ...

The origins and history of the study of teratology and developmental toxicology span centuries of human experience. Anatomical malformations observed at birth have been described across many generations but the root causes of these events have been enigmatic and difficult to unders ...

Oxidative stress has been recognized as a contributing factor in the toxicity of a large number of developmental toxicants. Traditional definitions of oxidative stress state that a shift in the balance between reduced and oxidized biomolecules within cells, in favor of the latter, result ...

We present two different methods for determining levels of glutathione in complex biological samples and plasma. The DTNB/GR enzyme recycling method is sensitive and requires no specialized equipment. The HPLC method is particularly useful for situations in which sample amounts are ...

Over the past decade, the use of gene expression profiling (i.e., toxicogenomics or transcriptomics) has been established as the vanguard “omics” technology to investigate exposure-induced molecular changes that underlie the development of disease. As this technology quickly ad ...