Xenobiotic influences on embryonic differentiation, growth and morphology in vitro

Schmid, B.

doi:10.3109/00498258509047433

Cited by 34 publications

(16 citation statements)

References 30 publications

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“…Sodium formate [116] yes Tween 80 [232] yes -Sodium nitroprusside [226] yes -Urethane [233] yes yes Styrene oxide [227] yes -Valproic acid [89] yes yes Thalidomide [228] yes yes 2-en-Valproic acid [89] no no Thymidine [167] no no 4-en-Valproic acid [89] yes -Tolbutamide [229] yes yes 4,4'-dien-Valproic acid [89] yes -Triazoles [146] yes -Vidarabinphosphat [177] yes -Trichlorethylene † [230] yes yes Vinblastine [167] yes yes…”

Section: In Vitro In Vivomentioning

confidence: 98%

“…Proven sensitivity of the WEC system to such a lead compound is the prerequisite for ranking the embryotoxic potential of its derivatives in vitro as demonstrated, for example, by valproic acid [115]. Acetone [167] no no Coumarin [167] yes yes Acetonitrile [168] yes yes Cyclohexylamine [189] yes * no Acetylsalicylic acid [169] yes yes Cyclophosphamide [190] yes * yes Acrolein [170] no -Cyclosporin A [167] no no Acrylonitrile [168] yes yes Cyproheptadine [191] yes yes Actinomycin D [167] yes yes L-Cysteine [167] no no Acyclovir [55] yes yes Cytochalasin D [192] yes no Adriamycin [171] yes yes 2'-Deoxyadenosine [55] no no Allopurinol [169] yes yes 2'-Deoxyguanosine [55] no no [196] no yes Atracurium [176] yes -Dideoxyinosine [196] no -Azathioprine [167] yes yes Di(2-ethylhexyl)phthalate [197] yes yes Azidothymidine [177] no yes Dimethylnitrosamine [167] no no Benzene † [178] yes * yes Dimethylsulfoxide [167] no no Benzylazoxyprocarbazine [179] yes -Doxorubicin [167] yes yes Bisphenol A [180] yes yes Edoferon kappa A [198] yes -Butylbenzylphthalate † [181] yes yes EDTA [167] no no n-Butyronitrile [168] yes -Epoxidized soy bean oil [193] no -Cadmium [182] yes yes Estrogens [199] yes - …”

Section: Test Strategies With the Wecmentioning

confidence: 99%

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Whole Embryo Culture: An Important Tool in Developmental Toxicology Today

Flick

Klug²

2006

CPD

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The number of candidate chemicals or drugs for registration and authorization is increasing at a fast rate and only few of the existing substances have been tested for teratogenicity to date. Therefore, there is high pressure on authorities to accept models like the whole embryo culture as a screening system for safety evaluation procedures. In view of this background the gradual development of the whole embryo culture into a standardized, scientifically validated tool for developmental toxicology during the last 70 years is summarized. The methodological development of the culture technique is described with the completion, improvement and refinement of the basic culture method as main intention. Special attention was paid to different culture techniques, culture media, gassing schedules, and evaluation strategies. Furthermore the importance of taking "in vitro pharmacokinetics" into consideration when a comparison of in vitro/in vivo results from embryotoxicity testing is intended, is stressed. Additionally, the demonstration of the broad spectrum of useful scientific applications when using this culture system in combination with sophisticated analytical techniques is demonstrated. Finally, an overview on different strategies for the validation of this culture system as an in vitro embryo toxicity test is provided and the officially accepted formal validation process for this application is summarized. The successful validation makes the whole embryo culture a complex in vitro embryotoxicity test with high accuracy and predictability. This robust in vitro system modelling the main phase of rodent organogenesis with a high reproducibility is valuable enough to attract special attention in related scientific fields.

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Section: In Vitro In Vivomentioning

confidence: 98%

Section: Test Strategies With the Wecmentioning

confidence: 99%

Whole Embryo Culture: An Important Tool in Developmental Toxicology Today

Flick

Klug²

2006

CPD

View full text Add to dashboard Cite

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“…In this simulated environment, it is possible to carry out various chemical and physical manipulations. The whole embryo culture (WEC) bioassay using mouse [43] and rat [44] embryos has been used for screening purposes for more than 20 years. Typically, the test molecule(s) can be added to the cultures for defined periods or for the entire culture period.…”

Section: Whole Embryo Culture Assaymentioning

confidence: 99%

Modeling Cardiovascular Development: New Approaches are Making In Vitro En Vogue

Goodwin¹,

Yost²,

Potts³

2006

CCR

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In vitro models have proven themselves to be powerful allies with in vivo models for the dissection of the molecular mechanisms of cardiovascular development. The purpose of this manuscript is to review the advances that have enabled the creation of a new generation of in vitro models. These advances include the advent of new biomaterials and cell scaffolds that have provided the opportunity to design niches where developmental processes can occur under controlled, in vitro conditions. The engineering of biomaterials, along with new imaging capabilities, are being applied to important developmental questions. These interdisciplinary approaches promise to accelerate the identification of the molecular processes that regulate the cell-cell and cell-extracellular matrix (ECM) interactions that occur during the development of cardiac tissues. These new models not only offer the opportunity to test molecular mechanisms but also provide morphogenetic assays where the development of functional cardiovascular tissues can be achieved. The advent of these technologies is far reaching: from the ability to engineer functional cardiovascular tissues to the rational implantation of cell therapies for cardiovascular disease.Key Words: Cardiac development, tissue engineering, in vitro models. PURPOSE AND SCOPEIn recent years, a great deal of progress has been made in determining many of the factors that regulate cardiovascular development. This progress has been accomplished through the use of both in vivo and in vitro models. Although in vivo models are critically important, their inherent complexity can confound experimental analysis. On the other hand, the advantage of in vitro models lies largely in the ability to control the number of experimental variables. Their application can be limited, however. These limitations are dependent on the fidelity to which they model the intended process. Recently described models presented in this review offer the ability to extend the applicability of in vitro models by making them more relevant to cardiovascular development in vivo.For the purposes of this review, in vitro development is defined as development that takes place under artificial conditions. This could be interpreted to include transgenic and knockout approaches; however, this review will exclude those techniques in which development occurs in utero. Likewise, models using Xenopus laevis and Zebrafish will not be discussed in detail. These models have added tremendously to the body of knowledge of cardiovascular biology but do not appear to require complex culturing techniques that will be discussed here. Why developing amniotes require specialized culture conditions is an intriguing question, but will not be addressed here. Specifically, we will focus on emerging in vitro models and how they can be used to investigate fundamental questions of cardiovascular development including coronary vessel development, the role of physical forces, fibroblast/myocyte interactions and late valve formation.This review is divided into thr...

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“…Actinomycin D (40) was apparently the most potent substance tested; it produced significant effects in cultured embryos at a concentration in the medium of 0.3 ng/mL. Ethanol (41) seemed to be the least active compound tested, since significant effects were observed only at medium concentrations above 2 mg/mL.…”

Section: Critical Reviewmentioning

confidence: 99%

“…Although whole embryo culture is being actively endorsed as a teratogen screen by several groups (40,65,67), only one of these groups (40) seems to have taken the necessary steps toward validation. All 18 ofthe known teratogens tested and 20 of the 21 nonteratogens tested were correctly classified.…”

Section: Critical Reviewmentioning

confidence: 99%

Teratological research using in vitro systems. I. Mammalian whole embryo culture.

Flynn¹

1987

Environ Health Perspect

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Approximately 390 literature references (through spring 1986) were reviewed for mammalian whole embryo culture procedures, with particular attention to the development of those cultures as systems for teratogenicity testing. The existing procedures could be conveniently divided into three groups, which are defined by the periods of embryogenesis that they embrace: preimplantation, peri-implantation, and postimplantation culture systems. The literature on peri-implantation embryo culture was sparse, and it did not appear that this procedure is being actively developed as a teratogen screening test. The extensive literature on both preimplantation and postimplantation embryo culture suggested considerable use of these two methods in evaluating embryotoxicants.The following discussion was compiled from information gleaned from all references. However, in the interest of brevity, only representative articles are specifically cited. Because the background and methodology for each system are distinct, each system will be discussed separately. Preimplantation Embryos IntroductionThe procedures for the culture of preimplantation mouse embryos from the two-cell to the blastocyst stage were developed in the late 1950s and early 1960s, primarily through the work of Whitten and Brinster (1). Kane (2) described conditions for culturing preimplantation rabbit embryos in a defined medium. Some success has been achieved in culturing preimplantation embryos from larger species, including human, but these species require undefined media that contain serum.Interest in preimplantation embryo culture as a screen for environmental teratogenesis arose from observations that preimplantation embryos, both in vivo and in vitro, are highly susceptible to the damaging effects of ionizing radiation. Simple procedures are available for obtaining metaphase chromosomal spreads from preimplantation embryos, thus making them ideal for studies on agents for which chromosomal damage is suspected of being the mechanism of reproductive toxicity. A literature search through spring 1986 revealed 53 references in which preimplantation embryos were used to evaluate the embryotoxicity of 48 different environmental agents. Preimplantation embryos from rats were used in one of these studies, and the remainder used embryos from mice. MethodologyBoth general methods of preimplantation mouse embryo culture (1) and methods applicable to teratology studies (3) have been reviewed and described. Female mice are both time-ovulated and superovulated with gonadotropins, mated to fertile males, and examined for vaginal plugs to confirm positive mating. Pregnant females are killed 36 hr after ovulation, the oviducts are excised, and two-cell stage embryos are flushed from the oviducts. Because of the hormonal superovulation, 20 to 40 embryos can be obtained from each female. The embryos are transferred to a chemically defined medium and incubated at 3700 in an atmosphere of 5% carbon dioxide in air. Cultured embryos develop normally for 72 hr up to the blastocyst sta...

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Xenobiotic influences on embryonic differentiation, growth and morphology in vitro

Cited by 34 publications

References 30 publications

Whole Embryo Culture: An Important Tool in Developmental Toxicology Today

Whole Embryo Culture: An Important Tool in Developmental Toxicology Today

Modeling Cardiovascular Development: New Approaches are Making In Vitro En Vogue

Teratological research using in vitro systems. I. Mammalian whole embryo culture.

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