Induction of Neural Tube Defects and Skeletal Malformations in Mice following Brief Hyperthermia in utero

Shiota, Kohei

doi:10.1159/000242767

Cited by 77 publications

(43 citation statements)

References 24 publications

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“…Most methods have involved elevation of the body temperatures of the mother, or of the maternal abdomen, at various stages of pregnancy and include the following: exposures in hot air chambers or incubators (Edwards 1967(Edwards , 1968aHartley et al, 1974;Hendrickx et al, 1979;Done et al, 1982), immersion of the lower abdomen in warm water (Chernoff et al,1985;Webster et al, 1985;Shiota 1988), immersion of the exteriorised pregnant uterus of anaes-thetised rats in warm water (Skreb and Frank, 1963), electromagnetic exposure (Lary et al, 1982;Brown-Woodman et al, 1988) and microwave irradiation of the abdomen and pregnant uterus (Fukui et al, 1992), maternal fever induced by the injection of boiled milk (Brinsmade and Rubsaamen, 1957) or endotoxins (Hellmann, 1977;Hilbelink, 1986) and administration of LSD to the mother (Freedman et al, 1981).…”

Section: Methods Of Induction and Conditions Causing H Y P E R T H E mentioning

confidence: 99%

“…Significant experimental demonstration of its teratogenic effects has been published for mice (Webster and Edwards, 1984;Finnell et al, 1986;Shiota, 1988), rats in vivo (Skreb and Frank,1963;Edwards, 1967;Lary, 1982;Germain et al , 1985;Webster et al, 1985) and in vitro (Cockroft and New, 1975;Mirkes, 1985;Walsh et al, 1985;Kimmel e t a l., 1993) guinea pigs (Edwards, 1969;Hutchinson and Bowler, 1984;Upfold et al, 1989) hamsters (Kilham and Ferm, 1976) sheep (Hartley et al, 1974), pigs (Done e t a l., 1982) and monkeys (Poswillo et al, 1974;Hendrickx et al , 1 9 7 9 ) .…”

Section: H I S T O R Ymentioning

confidence: 99%

“…Defects of the CNS can be severe and bizarre, such as anencephaly, exencephaly, encephalocele, microphthalmia or subtle such as various degrees of micrencephaly (Edwards, 1969b) associated with learning deficits (Lyle et al, 1977). The most sensitive period for neural tube defects (NTD) and microphthalmia is at the the neural plate stage of development, just prior to and during the early stages of tube closure, E8 in mice (Shiota, 1988), E9.5 in rats Walsh et al , 1987) and E13-14 in guinea pigs (Harding and Edwards, 1993) (Figure 1). The most sensitive stage for micrencephaly is just prior to and during formation of the cortical plate (E13-14 in rats and E21 in guinea pigs) and precedes the intense phase of neuroepithelial proliferation which produces the neurons of the cerebral cortex.…”

Section: Developmental Defects Caused By Hyperthermiamentioning

confidence: 99%

“…Neuroepithelial cell death was also the most notable feature in the developing CNS of heated E21 guinea pig embryos Wanner et al, 1976;Upfold et al ., 1989), as well as in E8 mouse (Shiota, 1988) and E14 rat embryos in vivo (Skreb and Frank, 1963;Harding and Edwards, 1993). and E9.5-10.5 rat embryos in culture (Mirkes, 1985;Walsh et al, 1987;1991;.…”

Section: Cell Death and Changes In The Cell Cycle After Exposure To Hmentioning

confidence: 99%

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Heat shock proteins and their role in early mammalian development

Walsh

Mj²,

Smith³

1997

Exp Mol Med

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A b s t r a c tElevated body temperature can result from many agents in the natural environment, such as fever, hot weather and heavy exercise. In our modern living conditions additional sources of induced hyperthermia including hot baths, saunas, drugs, electromagnetic radiation and ultrasound have been introduced. Hyperthermia during pregnancy has been shown to cause a wide spectrun of effects in all species studied, including humans, the outcome depending on the dose of heat absorbed by the mother and embryo and the stage of enbryonic or fetal development when exposed. The dose of heat is the product of the elevation of temperature above normal and the duration of the elevation. In relatively uncontrolled natural environmental exposures, embryonic death and resorption or abortion are probably the most common outcome. In less severe exposures (smaller doses) major or minor developmental defects can result and the central nervous system appears to be a major target for its effects. Heat damage to embryos appears to be by apoptotic and other forms of cell death in organs at critical stages of development. Over many millennia all living orgaisms appear to have developed protective m e c h a n i s m s against excess heat, known collectively as the heat shock response. This response has been s t u d i e d intensively over the last 20 years and its mechanisms of protection are now becoming more clearly defined. Exposures to heat (and a number of other toxic agents) trigger the heat shock response which is characterized by abrupt suspension in the normal protein synthesis and the concurrent induction of heat shock genes (hsp) and the synthesis of a set of protein families known collectively as the heat shock proteins (HSP). The hsp are known to be involved in the response in embryos, each has at least two copies, one which appears to have functions in the normal embryonic development (cognate) and another which is induced at a certain dose of heat (induced) and which can offer some protection against damage for some time after the initiating dose.

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Section: Methods Of Induction and Conditions Causing H Y P E R T H E mentioning

confidence: 99%

Section: H I S T O R Ymentioning

confidence: 99%

Section: Developmental Defects Caused By Hyperthermiamentioning

confidence: 99%

Section: Cell Death and Changes In The Cell Cycle After Exposure To Hmentioning

confidence: 99%

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Heat shock proteins and their role in early mammalian development

Walsh

Mj²,

Smith³

1997

Exp Mol Med

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“…Allerdings ist dabei zu berücksichtigen, dass die intravenöse Substanzgabe an Mäuse bei den Muttertieren Stress verursacht, wobei gerade bei der Maus Stress (wie Hitze) nachgewiesenermaßen schon alleine verschiedene Missbildungen (z. B. Gaumenspalten, Neuralrohrdefekte) bei den Nachkommen verursachen kann (Shiota 1988). Auch ist die tägliche Injektionsdauer nicht angegeben.…”

Section: -Pränatale Entwicklungstoxizitätunclassified

Acetaldehyd [MAK Value Documentation in German language, 2008]

2012

The MAK‐Collection for Occupational Health and Safety

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Veröffentlicht in der Reihe Gesundheitsschädliche Arbeitsstoffe , 44. Lieferung, Ausgabe 2008 Der Artikel enthält folgende Kapitel: Allgemeiner Wirkungscharakter Wirkungsmechanismus Toxikokinetik und Metabolismus Aufnahme, Verteilung, Ausscheidung Metabolismus Erfahrungen beim Menschen Einmalige Exposition Wiederholte Exposition Wirkung auf Haut und Schleimhäute Allergene Wirkung Reproduktionstoxizität Genotoxizität Kanzerogenität Tierexperimentelle Befunde und In‐vitro‐Untersuchungen Akute Toxizität Subakute, subchronische und chronische Toxizität Wirkung auf Haut und Schleimhäute Allergene Wirkung Reproduktionstoxizität Genotoxizität Kanzerogenität Sonstige Wirkungen Bewertung

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Teratogen update: Gestational effects of maternal hyperthermia due to febrile illnesses and resultant patterns of defects in humans

1998

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Hyperthermia was the first teratogen in animals that was subsequently proven to be teratogenic in humans. Animal studies have demonstrated heat to be a significant cause for reproductive problems in a wide variety of mammals. These problems range from embryonic death and abortion to teratogenically induced anomalies, and are heavily dependent on the dose and timing of the exposure (Edwards, '86; Edwards et al., '95). The threshold of effect in many species begins at about 1.5°C over normal core body temperature. In general, higher temperatures and/or longer durations are most likely to cause abortions, while lower elevations cause embryonic death and resorption, or abnormalities of embryogenesis, if exposure occurs at critical stages of development.The range of defects induced by hyperthermia in experimental animals includes: anencephaly/exencephaly, encephalocele (Webster and Edwards, '84; '92), micrencephaly (Edwards, '69b; Edwards et al., '84; Upfold et al., '89), microphthalmia, talipes, arthrogryposis, abdominal wall defects, and limb reduction defects (Edwards, '86). Such defects (Figs. 1, 2) have been induced by heat in a variety of mammals, including guinea pigs, hamsters, rats, mice, rabbits, sheep, pigs, monkeys, and humans (Edwards, '86), though the confounding effects of the febrile illnesses themselves and their therapies remain problematic in the interpretation of human data. Central nervous system (CNS) defects appear to be the most common consequence of hyperthermia in all species, and cell death or delay in proliferation of neuroblasts is believed to be one major explanation for these effects (Edwards et al., '74; Wanner et al., '75; Upfold et al., '89). Vascular disruption may also be involved in the pathogenesis of some defects of the CNS and other structures (Nilsen, '85; Webster et al., '87).In the human, heat-induced vascular disruption has been implicated in the pathogenesis of Moebius syndrome (Graham et al., '88; Lipson et al., '89), oroman-dibular-limb hypogenesis syndrome (Superneau and Wertelecki, '85), and the amyoplasia form of arthrogryposis (Ivarsson and Henriksson, '84; Edwards et al., '90). In this review, we confirm an association between febrile maternal illnesses and offspring born with these conditions, as well as other central nervous system problems. The nature of the specific associated anomalies appears to relate to the extent, duration, and timing of the maternal fever. These associated defects are similar to those induced experimentally in guinea pigs, monkeys, and a wide variety of other experimental animals (Hendrickx et al., '79; Edwards, '86; Edwards et. al., '95). BACKGROUND IN EXPERIMENTAL ANIMALSHyperthermia refers to an elevated body temperature. It has many causes, including febrile infections, hot/humid environments, and heavy exercise (especially in conditions of high heat and humidity), which may affect all species of animals. The normal physiological homeostatic mechanisms, which maintain body temperatures at relatively stable levels, may be altered or o...

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Induction of Neural Tube Defects and Skeletal Malformations in Mice following Brief Hyperthermia in utero

Cited by 77 publications

References 24 publications

Heat shock proteins and their role in early mammalian development

Heat shock proteins and their role in early mammalian development

Acetaldehyd [MAK Value Documentation in German language, 2008]

Teratogen update: Gestational effects of maternal hyperthermia due to febrile illnesses and resultant patterns of defects in humans

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