Comparison of the metabolic activity of yolk sac tissue in the whole embryo and isolated yolk sac culture

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

doi:10.1016/0890-6238(92)90025-o

Cited by 11 publications

(3 citation statements)

References 15 publications

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“…It also facilitates the transport of maternal lipids, cholesterol and other metabolites to the embryo until the embryonic liver can take over this function, and it is involved in haematopoiesis and gene regulation (Cindrova-Davies et al, 2017). Furthermore, the yolk sac metabolises teratogenic substances (Terlouw and Bechter, 1992). Disruption of yolk sac function causes embryonic malformation phenotypes that overlap with CNDD (Brent and Fawcett, 1998, Brent et al, 1971, Ornoy and Miller, 2023, Perez-Garcia et al, 2018), underscoring the yolk sac’s crucial role for normal embryo development.…”

Section: Discussionmentioning

confidence: 99%

Impaired yolk sac NAD metabolism disrupts murine embryogenesis with relevance to human birth defects

Bozon,

Cuny,

Sheng

et al. 2024

Preprint

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Severe congenital malformations are a frequent cause of premature death and morbidity in children worldwide. Malformations can originate from numerous genetic or non-genetic factors but in most cases the underlying causes are unknown. Genetic disruption of nicotinamide adenine dinucleotide (NAD) de novo synthesis drives the formation of multiple congenital malformations, collectively termed Congenital NAD Deficiency Disorder (CNDD), highlighting the necessity of this pathway during embryogenesis. Previous work in mice shows that NAD deficiency perturbs embryonic development specifically during a critical period when organs are forming. While NAD de novo synthesis is predominantly active in the liver postnatally, the site of activity prior to and during organogenesis is unknown. Here, we used a mouse model of human CNDD and applied gene expression, enzyme activity and metabolic analyses to assess pathway functionality in the embryonic liver and extraembryonic tissues. We found that the extra-embryonic visceral yolk sac endoderm exclusively performs NAD de novo synthesis during early organogenesis before the embryonic liver takes over this function. Furthermore, under CNDD-inducing conditions, mouse visceral yolk sacs had reduced NAD levels and altered NAD-related metabolic profiles which affected embryo metabolism. Expression of requisite genes for NAD de novo synthesis is conserved in the equivalent yolk sac cell type in humans. Our findings show that visceral yolk sac-mediated NAD de novo synthesis activity is essential for mouse embryonic development and perturbation of this pathway results in CNDD. Given the functional homology between mouse and human yolk sacs, our data improve the understanding of human congenital malformation causation.

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Section: Discussionmentioning

confidence: 99%

Impaired yolk sac NAD metabolism disrupts murine embryogenesis with relevance to human birth defects

Bozon,

Cuny,

Sheng

et al. 2024

Preprint

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show abstract

“…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%

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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“…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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Comparison of the metabolic activity of yolk sac tissue in the whole embryo and isolated yolk sac culture

Cited by 11 publications

References 15 publications

Impaired yolk sac NAD metabolism disrupts murine embryogenesis with relevance to human birth defects

Impaired yolk sac NAD metabolism disrupts murine embryogenesis with relevance to human birth defects

Rat Embryo Cultures for In Vitro Teratology

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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