Mode of Action: Yolk Sac Poisoning and Impeded Histiotrophic Nutrition—HBOC-Related Congenital Malformations

Holson, Joseph F.; Stump, Donald G.; Pearce, L. Bruce; Watson, Rebecca; DeSesso, John M.

doi:10.1080/10408440591007412

Cited by 29 publications

(16 citation statements)

References 16 publications

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“…More recent WEC research by Ambroso and Harris has suggested that the mechanism by which the anti-malarial drug and in vivo teratogen, chloroquine, acts is via reversible inhibition of cysteine proteinase cathepsin B and L activity (Ambroso and Harris, 1994). These studies on histiotrophic nutrition are critically important for human risk assessment, as there is considerable evidence suggesting that this mechanism occurs only in species that rely on an inverted yolk sac placenta during organogenesis, but not in humans and other primates that utilize a chorioallantoic placenta throughout gestation (Beck, 1976;Carney et al, 2004;Holson et al, 2005).…”

Section: Yolk Sac As a Target For Teratogenesismentioning

confidence: 97%

“…This key early placental nutrition transfer pathway involves endocytic uptake of proteins by the visceral yolk sac, degradation by lysosomal cysteine proteases, and delivery of amino acids to the embryo via the vitelline circulation. The classic compound acting via this mechanism is trypan blue, although other agents acting similarly include anti-VYS antibodies, anti-laminin antibodies, somatomedin inhibitors, a class of compounds known as hemoglobin-based oxygen carriers, dextran, and chloroquine (Brent et al, 1990;Chambers et al, 1995;Fisher, 1981;Holson et al, 2005;Hunter et al, 1991).…”

Section: Yolk Sac As a Target For Teratogenesismentioning

confidence: 98%

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Whole embryo culture: a “New” technique that enabled decades of mechanistic discoveries

Ellis-Hutchings

Carney

2010

Birth Defects Research Pt B

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Denis New's development of the rodent whole embryo culture (WEC) method in the early 1960s was a groundbreaking achievement that gave embryologists and teratologists an unprecedented degree of access to the developing postimplantation rodent embryo. In the five decades since its development, WEC has enabled detailed investigations into the regulation of normal embryo development as well as a plethora of research on mechanisms of teratogenesis as induced by a wide range of agents. In addition, WEC is one of the few techniques that has been validated for use in teratogenicity screening of drugs and chemicals. In this review, we retrace the steps leading to New's development of WEC, and highlight many examples in which WEC played a crucial role leading to important discoveries in teratological research. The impact of WEC on the field of teratology has been enormous, and it is anticipated that WEC will remain a preferred tool for teratologists and embryologists seeking to interrogate embryo development for many years to come.

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Section: Yolk Sac As a Target For Teratogenesismentioning

confidence: 97%

Section: Yolk Sac As a Target For Teratogenesismentioning

confidence: 98%

Whole embryo culture: a “New” technique that enabled decades of mechanistic discoveries

Ellis-Hutchings

Carney

2010

Birth Defects Research Pt B

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“…O saco vitelino invertido de roedores desempenha vá-rias funções podendo-se destacar aquelas relacionadas ao armazenamento, absorção e transferência de nutrientes (Laliberté et al 1984, Carter 2001, Holson et al 2005, Favaron et al 2012. De fato, distúrbios nestas funções produzidas por agentes teratogênicos, por exemplo, podem explicar possíveis doenças no recém-nascido (Jollie 1990).…”

Section: Introductionunclassified

Dinâmica da inversão do saco vitelino em preás (Galea spixii Wagler, 1831)

et al. 2013

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Pesq. Vet. Bras. 33(8) The aim of this study was to study the time of yolk sac inversion as well as the dynamics resulting from this process in galea throughout pregnancy. For this, conventional histological techniques, scanning electron microscopy and transmission electron microscopy were used. Parietal and visceral endoderm delimiting the yolk sac cavity was observed at 12 days of pregnancy. The parietal endoderm was coating the fetal surface of the chorioallantoic placenta as well as delimiting the decidua capsularis area. This endoderm had prismatic format and were apart from the trophoblast by an enlarged Reichert's membrane. The visceral endoderm had vitelline vessels and there were villi only in certain areas. At 14 days of pregnancy the yolk sac inversion was characterized by the degeneration of parietal endoderm and mural trophoblast, and also the gradual disappearance of the Reichert's membrane. So it made the visceral endoderm establish an interface with the uterine epithelium. After the inversion, the parietal endoderm which remained intact was the one that rested on the chorioallantoic placenta surface. It presented cells with high columnar format and pseudostratified epithelium featured. The visceral endoderm presented many apical villi, especially in areas close to the chorioallantoic placenta. The continued development of the embryo and chorioallantoic placenta evidenced the emergence of an important apposition area between visceral and parietal endoderm. The yolk sac inversion represented an anatomical arrangement in favor of the embryo development as well as an evolutionary trait in this rodent species.INDEX TERMS: Galea, Galea spixii, yolk sac, visceral endoderm, parietal endoderm, inversion.

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“…The mode of action (MoA) for several adverse developmental outcomes has been determined , Foster 2005, Holson et al 2005, Kavlock and Cummings 2005. The regulatory guideline and MoA toxicity studies with sulfoxafl or described above revealed fi ndings for which an MoA had not previously been described (Rasoulpour et al 2012).…”

Section: Dammentioning

confidence: 99%

“…Recent eff orts have also been directed toward extending the MoA approach to non-cancer MoA analyses , Foster 2005, Holson et al 2005, Kavlock and Cummings 2005, with several addressing human relevance. Standardization of the approach has also been recommended by the IPCS (Boobis et al 2008).…”

Section: Dammentioning

confidence: 99%

Human relevance framework evaluation of a novel rat developmental toxicity mode of action induced by sulfoxaflor

Ellis-Hutchings

Rasoulpour

Terry³

et al. 2014

Critical Reviews in Toxicology

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Sulfoxafl or (CAS# 946578-00-3) is a novel active substance with insecticidal properties mediated via its agonism on the highly abundant insect nicotinic acetylcholine receptor (nAChR). In developmental and reproductive toxicity studies, gestational exposure caused fetal abnormalities (primarily limb contractures) and reduced neonatal survival in rats, but not rabbits, following high-dose dietary exposure. Sulfoxafl or induced these eff ects via a novel mode of action (MoA) mediated by the fetal-type muscle nAChR with the following key events: (1) binding to the receptor, (2) agonism on the receptor, causing (3) sustained muscle contracture in the near-term fetus and neonatal off spring. This sustained muscle contracture results in misshapen limbs, bent clavicles, and reduced diaphragm function, which compromises respiration in neonatal rats at birth, reducing their survival. This review evaluates the weight of evidence for this MoA based upon the Bradford Hill criteria, includes a cross-comparison of applied and internal doses in a variety of in vitro , ex vivo , and in vivo study designs, examines alternative MoAs, and applies a Human relevance framework (HRF) to ascertain human risk for this rat MoA. The review indicated, with a high level of confi dence, that the sulfoxafl or-induced fetal abnormalities and neonatal death in rats occur via a single MoA comprising sustained activation of the rat fetal-type muscle nAChR resulting in a sustained muscle contracture. This MoA is considered not relevant to humans, given fundamental qualitative diff erences in sulfoxafl or agonism on the rat versus the human muscle nAChR. Specifi cally, sulfoxafl or does not cause agonism on either the human fetal-or adult-type muscle nAChR.

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Mode of Action: Yolk Sac Poisoning and Impeded Histiotrophic Nutrition—HBOC-Related Congenital Malformations

Cited by 29 publications

References 16 publications

Whole embryo culture: a “New” technique that enabled decades of mechanistic discoveries

Whole embryo culture: a “New” technique that enabled decades of mechanistic discoveries

Dinâmica da inversão do saco vitelino em preás (Galea spixii Wagler, 1831)

Human relevance framework evaluation of a novel rat developmental toxicity mode of action induced by sulfoxaflor

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