Developmental neurotoxicity: do similar phenotypes indicate a common mode of action? A comparison of fetal alcohol syndrome, toluene embryopathy and maternal phenylketonuria

Costa, Lucio G.; Guizzetti, Marina; Burry, M.; Oberdoerster, Jan

doi:10.1016/s0378-4274(01)00501-x

Cited by 47 publications

(27 citation statements)

References 62 publications

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“…In addition, pericardial cavity inflation was detected. All these features were in accordance with the previously reported characteristics of FAS (Samson, 1986;Qu et al, 2000;Costa et al, 2002). Figure 2 shows some representative malformations found in the alcohol-exposed embryos.…”

Section: Morphological Examination Dna and Protein Contentssupporting

confidence: 90%

Effect of ethanol on the development of visceral yolk sac

Xiao

2005

Human Reproduction

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BACKGROUND: Prenatal ethanol exposure can cause development retardation and malformations in human offspring. Before the formation of chorioallantoic placenta, yolk sac plays an important role in transporting nutrients from the mother to the embryo. Functional suppression of yolk sac is found to be relevant to the malformations in mammalian embryos. METHODS: Female 8.5-day C57BL/6J mouse embryos were cultured in vitro and exposed to different doses of ethanol. The development of visceral yolk sac (VYS) was examined with light and electron microscopes. The expression profiles of some vasculogenesis-related genes were detected with reverse transcription -PCR. RESULTS: A dose-dependent toxicity to the VYS was found, including reduced diameter, decreased protein and DNA contents, and suppressed development of vitelline vessels. The hypogenesis of VYS agreed with the retarded development and/or malformations found in the embryos. Histological and functional alterations were found in the ethanol-exposed VYS endodermal cells. The expressions of vasculogenesis-related genes, fetal liver kinase 1 (Flk1) and tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 2 (Tie2), were repressed by ethanol. CONCLUSIONS: Impaired structural and functional development of VYS may contribute to the teratogenic action of ethanol in mice, which may also provide a clue to the study of fetal alcohol syndrome in humans.

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Section: Morphological Examination Dna and Protein Contentssupporting

confidence: 90%

Effect of ethanol on the development of visceral yolk sac

Xiao

2005

Human Reproduction

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“…These children exhibited many prenatal toluene-associated craniofacial abnormalities, growth retardation, and CNS dysfunction as well as malformations of the brain, mental retardation, microencephaly, attention deficits, and hyperactivity [Pearson et al 1994], all of which are also seen in children with FASDs [Kodituwakku 2007]. This study, as well as others, has documented parallel outcomes including facial dysmorphology (e.g., hypoplasia of the midface, small palpebral fissures, thin upper lip), perinatal growth, and neurobehavioral delay [Stoler 1999;Costa et al 2002]. Toluene embryopathy may be the best candidate for a ''phenocopy'' of FAS.…”

Section: Is There a Fetal Solvent Syndrome?supporting

confidence: 53%

“…While congenital abnormalities have been reported following long-term exposure to low levels of toluene modeling occupational settings [Costa et al 2002], to the authors' knowledge there has only been one study to examine gross dysmorphology, after repeated, highdose binge patterns of prenatal toluene exposure. Bowen and colleagues [2009] examined the preweaning developmental effects of prenatal exposure to toluene (8,000-16,000 ppm; 30 min, 2 times/day, GD8 through GD20) and reported significant increases in the occurrence of soft tissue anomalies and skeletal abnormalities, including reduced skeletal ossification.…”

Section: Pregnancy Outcomesmentioning

confidence: 99%

Reproductive Toxicology and Teratology of Abused Toluene

Hannigan

Bowen

2010

Systems Biology in Reproductive Medicine

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Reproductive Toxicology and Teratology of Abused TolueneToluene is an organic solvent that is widely used by industry and is ubiquitous in our environment. As a result, exposure to solvents like toluene in workrelated settings (i.e., relatively constant, low-level exposures) or through inhalant abuse (i.e., relatively intermittent, high-level exposures) is increasing for many women of reproductive age. Evidence suggests that the risk for pregnancy problems, as well as developmental delays and neurobehavioral difficulties, is higher for the children of women who have been exposed to high concentrations of organic solvents during pregnancy than for those who have not. These risks appear to be higher in cases of abuse exposure to solvents such as toluene, particularly in comparison to the risk for teratogenic outcomes with occupational solvent exposure. Despite this, the reproductive toxicology and teratology following abuse of toluene and other inhalants remains under-investigated. This brief review describes the current state of our understanding of the reproductive and teratogenic risk of gestational toluene abuse. The data to date suggest that the high levels of toluene exposure typical with inhalant abuse are more detrimental to fetal development than typical occupational exposure, and preclinical paradigms can be beneficial for investigating the processes and risks of prenatal solvent exposure. While substantial research has been done on the reproductive effects of occupational exposures to organic solvents, more research is needed on the outcomes and mechanisms of exposures typical of inhalant abuse.

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“…The effects seen in humans developmentally exposed to toluene are strikingly similar to those observed in the fetal alcohol syndrome (FAS) [Pearson et al, 1994;Costa et al, 2002]; indeed, Toutant and Lippman [1979] reported their case as fetal solvent syndrome. Animal models of FAS have often utilized postnatal exposure to ethanol.…”

Section: Introductionmentioning

confidence: 81%

Developmental Neurotoxicity of Toluene: in vivo and in vitro Effects on Astroglial Cells

et al. 2003

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Toluene, an inexpensive and available industrial solvent, has become increasingly popular as a drug of abuse. Inhaling toluene leads to a feeling of euphoria and several reports have shown that children born to women who had abused toluene during pregnancy present a syndrome (toluene embryopathy or fetal solvent syndrome) that is characterized by CNS effects (e.g. microencephaly), growth retardation and facial dysmorphologies. The characteristics of the fetal solvent syndrome are very similar to those observed in the fetal alcohol syndrome. As exposure of rats to ethanol during the brain growth spurt has been shown to cause microencephaly and to affect glial cell proliferation and maturation, the present study examines the effects of toluene administration (250, 500 and 750 mg/kg) in neonatal rats from postnatal day 4 to 10. This treatment resulted in a significant decrease in both brain and body weights, and in a significant reduction of levels of glial fibrillary acidic protein, but not of neuron-specific enolase in rat brain. In vitro experiments demonstrate that pharmacologically relevant concentrations of toluene (250–1,000 µM) significantly inhibit proliferation of rat cortical astrocytes without causing overt cytotoxicity. These results indicate that toluene does not cause selective microencephaly; however, it affects brain weight, and appears to target developing astrocytes, possibly by inhibiting their proliferation.

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Developmental neurotoxicity: do similar phenotypes indicate a common mode of action? A comparison of fetal alcohol syndrome, toluene embryopathy and maternal phenylketonuria

Cited by 47 publications

References 62 publications

Effect of ethanol on the development of visceral yolk sac

Effect of ethanol on the development of visceral yolk sac

Reproductive Toxicology and Teratology of Abused Toluene

Developmental Neurotoxicity of Toluene: in vivo and in vitro Effects on Astroglial Cells

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