Effects of Prenatal Ethanol Exposure on Postnatal Growth and the Insulin-Like Growth Factor Axis

Aros, Sofía; Mills, James L.; Íñiguez, Germán; Ávila, Alejandra; Conley, Mary; Troendle, James; Cox, Christopher; Cassorla, Fernando

doi:10.1159/000319706

Cited by 37 publications

(25 citation statements)

References 65 publications

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“…In both human and animal studies, specific environmental exposures, including bisphenol-A, cigarette smoke and ethanol, have been linked to genomic imprinting alterations in various tissues (Aros et al, 2011;Haycock and Ramsay, 2009;Murphy et al, 2012;Prins et al, 2008;Stouder et al, 2011;Zhang et al, 2012). Dietary factors, specifically folate supplementation in pregnant women, have been linked to reduced methylation of the imprinted IGF2 gene's ICRs in cord blood, an effect most pronounced in male infants (Hoyo et al, 2011).…”

Section: Genomic Imprintingmentioning

confidence: 99%

Influence of environmental exposure on human epigenetic regulation

Marsit

2015

Journal of Experimental Biology

195

119

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Environmental toxicants can alter epigenetic regulatory features such as DNA methylation and microRNA expression. As the sensitivity of epigenomic regulatory features may be greatest during the in utero period, when critical windows are narrow, and when epigenomic profiles are being set, this review will highlight research focused on that period. I will focus on work in human populations, where the impact of environmental toxicants in utero, including cigarette smoke and toxic trace metals such as arsenic, mercury and manganese, on genome-wide, gene-specific DNA methylation has been assessed. In particular, arsenic is highlighted, as this metalloid has been the focus of a number of studies and its detoxification mechanisms are well understood. Importantly, the tissues and cells being examined must be considered in context in order to interpret the findings of these studies. For example, by studying the placenta, it is possible to identify potential epigenetic adaptations of key genes and pathways that may alter the developmental course in line with the developmental origins of health and disease paradigm. Alternatively, studies of newborn cord blood can be used to examine how environmental exposure in utero can impact the composition of cells within the peripheral blood, leading to immunological effects of exposure. The results suggest that in humans, like other vertebrates, there is a susceptibility for epigenomic alteration by the environment during intrauterine development, and this may represent a mechanism of plasticity of the organism in response to its environment as well as a mechanism through which long-term health consequences can be shaped.

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Section: Genomic Imprintingmentioning

confidence: 99%

Influence of environmental exposure on human epigenetic regulation

Marsit

2015

Journal of Experimental Biology

195

119

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“…Children who were exposed to ethanol in utero were found to secrete less growth hormone than non-exposed children of normal body size, but of comparable levels to non-exposed small-for-gestational-age children (Hellström et al, 1996). Furthermore, there was a greater increase in the levels of insulin-like growth factor I (IGF-I) in prenatally ethanol-exposed children at age 3 and 4 when compared to non-exposed children (Aros et al, 2011). In this study, there was a correlation between IGF-I levels and body size (body mass index, height, and weight) in the healthy children at age three; however, this correlation between IGF-I and body size was lost in the ethanol-exposed children at age three (Aros et al, 2011), suggesting that not only did prenatal ethanol exposure perturb IGF-I levels, but the ethanol exposure was also able to perturb the relationship between IGF-I and body size (Aros et al, 2011).…”

Section: Potential Mechanisms Underlying Ethanol-induced Growth Restrmentioning

confidence: 99%

“…Furthermore, there was a greater increase in the levels of insulin-like growth factor I (IGF-I) in prenatally ethanol-exposed children at age 3 and 4 when compared to non-exposed children (Aros et al, 2011). In this study, there was a correlation between IGF-I levels and body size (body mass index, height, and weight) in the healthy children at age three; however, this correlation between IGF-I and body size was lost in the ethanol-exposed children at age three (Aros et al, 2011), suggesting that not only did prenatal ethanol exposure perturb IGF-I levels, but the ethanol exposure was also able to perturb the relationship between IGF-I and body size (Aros et al, 2011). The rate of postnatal growth of mice lacking a functional copy of IGF-1 was reduced when compared with wildtype mice (Baker et al, 1993), suggesting that a deficiency in IGF-1 is likely to lead to growth restriction.…”

Section: Potential Mechanisms Underlying Ethanol-induced Growth Restrmentioning

confidence: 99%

“…The rate of postnatal growth of mice lacking a functional copy of IGF-1 was reduced when compared with wildtype mice (Baker et al, 1993), suggesting that a deficiency in IGF-1 is likely to lead to growth restriction. However, it is presently unknown what effect an over-expression of IGF-1, such as that observed by Aros et al, 2011, has on growth. Prenatal ethanol exposure has consequences on both preand postnatal growth; however, the exact mechanism behind this is poorly understood.…”

Section: Potential Mechanisms Underlying Ethanol-induced Growth Restrmentioning

confidence: 99%

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A study of the consequences of early gestational ethanol and/or nicotine exposure in the mouse

Yamada¹

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The in utero environment is a critical determinant of the immediate and future health of the developing fetus. In Australia, two of the most commonly used drugs during pregnancy are alcohol and nicotine. Prolonged periods of gestational exposure to alcohol and nicotine, separately, have been associated with a range of adverse outcomes in the offspring, in both humans and experimental animal models. The consequences of ethanol and nicotine exposure restricted to early gestation on resultant offspring are poorly characterised, and few animal models exist to build greater understanding. Moreover, the immediate molecular changes associated with exposures to ethanol and/or nicotine restricted to early gestation has yet to be described.This thesis utilised mouse models of early gestational ethanol and/or nicotine exposure to explore the impact of each of these exposures on offspring growth, as well as their associated transcriptional and epigenetic changes. In each model, pregnant C57BL/6 dams were provided with ad libitum access to solutions of 10% ethanol and/or 100 µg/ml nicotine from fertilisation (0.5 dpc) to midgestation (8.5 dpc). The exposure window utilised in each of the models is developmentally equivalent to the first three to four weeks of a human pregnancy.Previously, our laboratory identified reduced growth, microcephaly, and gene expression changes in the liver and hippocampus of the postnatal offspring of the model of prenatal ethanol exposure utilised in this thesis. In contrast, at mid-gestation (9.5 dpc), there was no evidence of developmental delay (somite number), reduced growth (crown-rump length), or microcephaly.Further, a genome-wide gene expression microarray (targeting 30 855 genes) and a screen of the expression of 641 microRNAs, identified only one gene (Bcl11b) as differentially expressed in male 9.5 dpc whole embryos following the ethanol exposure. These data suggest that there is a delay between the ethanol exposure and the onset of adverse phenotypes -arguing that the embryo is somehow able to form a memory of the ethanol exposure. The absence of widespread transcriptional changes suggests that changes in embryonic mRNA and microRNA expression are unlikely to be major contributors to the memory of the exposure.A early gestational model of nicotine exposure was newly established in this thesis. This nicotine exposure resulted in an average serum cotinine (metabolite of nicotine) concentration similar to that reported in humans who smoke 10 to 15 cigarettes per day. This exposure was sufficient to induce a reduction in body size both at mid-gestation and postnatally, but not at late gestation. Furthermore, the increased expression of Zscan10 in the whole male 9.5 dpc embryo was identified and validated across multiple cohorts. Zscan10 encodes for a transcription factor expressed throughout development, with a proposed role in the regulation of progenitor cells. The increased expression of Zscan10 in the nicotine-exposed embryos was associated with a reduction in DNA methylation ...

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“…Signifikanter Alkoholkonsum, der in funktionell-neurologischen Auffälligkeiten des Kindes resultiert, wurde in den Publikationen sehr unterschiedlich definiert [3,7,8,17,27,30,32] zwischen einem Getränk/Tag [19], mindestens 5 Getränken zu einem Anlass [5,13,23], 10 Getränken/Woche oder 45 Geträn-ken/Monat [17].…”

Section: Alkoholkonsumunclassified

Mütterlicher Alkoholkonsum in der Schwangerschaft und fetales Alkoholsyndrom

Landgraf

Hilgendorff

Heinen

2014

Monatsschr Kinderheilkd

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Risikofaktoren und ihre Bedeutung in der Prävention und frühen DiagnoseAlkoholkonsum der werdenden Mutter während der Schwangerschaft ist häufig und kann das ungeborene Kind gravierend schädigen. Die intrauterinen Schädigungen des kindlichen Gehirns sind biologisch irreversibel und führen zu lebenslangen und vielfältigen Beeinträchtigungen der betroffenen Menschen, ihrer Familien und ihrer Umgebung. Die Kenntnis von Risikofaktoren für Alkoholkonsum in der Schwangerschaft und für die Entstehung eines fetalen Alkoholsyndroms (FAS) erleichtert die täg-liche klinisch-ärztliche Praxis und verbessert, laut klinischer Erfahrung, die Primär-sowie Sekundärprävention betroffener Familien.

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Effects of Prenatal Ethanol Exposure on Postnatal Growth and the Insulin-Like Growth Factor Axis

Cited by 37 publications

References 65 publications

Influence of environmental exposure on human epigenetic regulation

Influence of environmental exposure on human epigenetic regulation

A study of the consequences of early gestational ethanol and/or nicotine exposure in the mouse

Mütterlicher Alkoholkonsum in der Schwangerschaft und fetales Alkoholsyndrom

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