Xenobiotic metabolism in the isolated conceptus

Bechter, R.; Terlouw, G.D.C.

doi:10.1016/0887-2333(90)90104-2

Cited by 9 publications

(4 citation statements)

References 18 publications

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“…It is especially important that methodologies and animal strains be held constant in screening studies. In these ways, it is possible to employ accumulated historical control and experimental data (Bechter and Terlouw, 1990) and compare test results from different experiments for compound development.…”

Section: Whole-embryo Culture In Industrial Teratogen Screeningmentioning

confidence: 99%

“…For example, by adding conditioned medium from hepatocyte cultures containing drug and metabolites to culture medium (sequential hepatocyte/whole‐embryo culture, Bechter et al, ), metabolites may be present during the extended culture period. Metabolic capacities of the embryo, per se, and especially those of the yolk sac, are active in vitro during the culture period (Bechter and Terlouw, ; Terlouw and Bechter, , ; Jones et al, ) and such metabolism may result in the formation of teratogenically relevant metabolites. Finally, because there is little information on the transfer of drugs and their metabolites from mother to fetus, those metabolites generated by these various systems may poorly represent actual exposures in vivo.…”

Section: Commentarymentioning

confidence: 99%

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Rat Embryo Cultures for In Vitro Teratology

2000

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Mammalian embryos provide a particular challenge to those who wish to study developmental processes because development takes place inside the mother's body, thus limiting the investigator's ability to directly affect and observe the embryonic stages of development. Fortunately, as this unit illustrates, methods have been developed for in vitro culture of rodent embryos during early postimplantation (gestation days 9 to 11) and early fetal (gestation days 12 to 14) stages, which are the periods during which the major systems of the embryo are established. Embryos at these stages are particularly suitable for screening studies to determine the effects of teratological agents.

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Section: Whole-embryo Culture In Industrial Teratogen Screeningmentioning

confidence: 99%

Section: Commentarymentioning

confidence: 99%

Rat Embryo Cultures for In Vitro Teratology

2000

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“…phenoxazone ethers [27]. However, these studies demonstrated that the yolk sac and not the embryonic tissues possess the main metabolizing capacity [28]. This statement is not limited to the situation of the p450 isoenzymes; it may be true for other enzymes such as peroxydases [29].…”

Section: Introductionmentioning

confidence: 98%

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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“…These metabolites, but not the parent compound QAB, accumulated in tissues of the cultured conceptuses. The visceral yolk sac was identified as the major site of conceptal bioconversion of QAB in vitro between prenatal d 10 and 13 [2,3].…”

Section: Introductionmentioning

confidence: 99%

Effects of QA 208‐199 and its metabolite 209‐668 on embryonic development in vitro after microinjection into the exocoelomic space or into the amniotic cavity of cultured rat conceptuses

Bechter

Terlouw²,

Lee

et al. 1991

Teratog Carcinog Mutagen

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The objective of this study was to determine the direct embryotoxic effects in vitro of N-hydroxy-N-methyl-7-propoxy-2-naphthalene-ethanamine (QA 208-199, QAB) and of one of its metabolites, 7-propoxy-naphthalene-2-ylacetic acid (209-668, QAA), after circumventing the bioconverting conceptual membranes. The compounds were, therefore, microinjected either into the exocoelomic space or into the amniotic cavity of rat conceptuses of 10 d at prenatal age at doses of up to 84.9 ng (QAA) and 180 ng (QAB) per conceptus respectively. The conceptuses were subsequently cultured for 28 h after which their development was assessed. QAB produced marginal effects on embryonic differentiation only after microinjection of the compound into the amniotic cavity. Dysmorphogenic effects, however, occurred in a dose-dependent fashion after either exocoelomic or intraamniotic microinjections of the compound. The frequencies and types of anomalies were similar after either exposure route and consisted predominantly of anomalies associated with axial rotation. QAA also impaired embryonic differentiation at only the high dose level of 84.9 ng per embryo and after intraamniotic injections only. Dysmorphogenic effects were observed in all experimental groups, although the differences were not statistically significant when compared with the concomitant controls. An increased proportion of anomalies observed were in the cephalic region as compared to the defects produced by QAB. These data suggest that QAA most probably is not the QAB metabolite responsible for the embryotoxic action of QAB in vitro. Furthermore, the results tend to confirm the suggested involvement of the visceral yolk sac membrane in mediating QAB embryotoxicity.

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Xenobiotic metabolism in the isolated conceptus

Cited by 9 publications

References 18 publications

Rat Embryo Cultures for In Vitro Teratology

Rat Embryo Cultures for In Vitro Teratology

Whole Embryo Culture: An Important Tool in Developmental Toxicology Today

Effects of QA 208‐199 and its metabolite 209‐668 on embryonic development in vitro after microinjection into the exocoelomic space or into the amniotic cavity of cultured rat conceptuses

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