Postnatal growth restriction and gene expression changes in a mouse model of fetal alcohol syndrome

Kaminen‐Ahola, Nina; Ahola, Arttu; Flatscher-Bader, Traute; Wilkins, Sarah J.; Anderson, Gregory J.; Whitelaw, Emma; Chong, Suyinn

doi:10.1002/bdra.20729

Cited by 37 publications

(40 citation statements)

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“…Bcl11b encodes for a transcription factor with roles in embryonic tooth development (Katsuragi et al, 2013) and the development of T lymphocytes (Wakabayashi et al, 2003). It was not identified to be differentially expressed in any of the other tissues previously assayed in this ethanol model (Kaminen-Ahola et al, 2010a;Marjonen et al, 2015;Zhang et al, 2015), nor has it been identified in association with other models of prenatal ethanol exposure. Consequently, the differential expression of Bcl11b following ethanol exposure has not been further characterised in this project.…”

Section: Discussionmentioning

confidence: 88%

“…These findings, while perhaps unsurprising given the absence of any apparent phenotype at 9.5 dpc, are seemingly at odds with those using the same ethanol model that identified numerous phenotypic outcomes and changes in the expression of various mRNAs and miRNAs in the adolescent and adult offspring (Kaminen-Ahola et al, 2010a;Marjonen et al, 2015;Zhang et al, 2015). Slc17a6 is one of the genes previously identified to be differentially expressed in the adult male hippocampus in the ethanol model .…”

Section: Discussionmentioning

confidence: 90%

“…Furthermore, despite an ethanol-associated postnatal phenotype of microcephaly (Kaminen-Ahola et al, 2010a), head size at 9.5 dpc was still proportionate to overall body size following the ethanol exposure (Figure 4.2B).…”

Section: Characterisation Of Growth Phenotypementioning

confidence: 97%

“…The exposure window utilised in this model is developmentally equivalent to the first 3 -4 weeks of a human pregnancy (Otis and Brent, 1954) -well before most Australian women will confirm their pregnancies (Callinan and Room, 2012). It has previously been identified using this model, that ethanol exposure even when restricted to this very early time in pregnancy was sufficient to result in changes to behaviour (Sanchez Vega et al, 2013), brain structure (Marjonen et al, 2015), craniofacial morphology (Kaminen-Ahola et al, 2010b), and postnatal growth (Kaminen-Ahola et al, 2010a).…”

Section: Consequences Of Early Gestational Exposure To Ethanol And/ormentioning

confidence: 99%

“…Prenatal exposure to ethanol, tobacco smoke and nicotine have been extensively associated with reduced offspring growth (Aliyu et al, 2009;Kaminen-Ahola et al, 2010a;Rowell and Clark, 1982;Wang et al, 2008Wang et al, , 2009). Furthermore, both maternal ethanol consumption (Kaminen-Ahola et al, 2010a) and maternal smoking (Delpisheh et al, 2008) have also been reported to result in microcephaly.…”

Section: Introductionmentioning

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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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 90%

Section: Characterisation Of Growth Phenotypementioning

confidence: 97%

Section: Consequences Of Early Gestational Exposure To Ethanol And/ormentioning

confidence: 99%

Section: Introductionmentioning

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 effects of alcohol on fetal development

Jones

2011

Birth Defects Research Pt C

131

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Prenatal exposure to alcohol has profound effects on many aspects of fetal development. Although alterations of somatic growth and specific minor malformations of facial structure are most characteristic, the effects of alcohol on brain development are most significant in that they lead to substantial problems with neurobehavioral development. Since the initial recognition of the fetal alcohol syndrome (FAS), a number of important observations have been made from studies involving both humans and animals. Of particular importance, a number of maternal risk factors have been identified, which may well be of relevance relative to the development of strategies for prevention of the FAS as well as intervention for those who have been affected. These include maternal age >30 years, ethnic group, lower socioeconomic status, having had a previously affected child, maternal under-nutrition, and genetic background. The purpose of this review is to discuss these issues as well as to set forth a number of questions that have not adequately been addressed relative to alcohol's effect on fetal development. Of particular importance is the critical need to identify the full spectrum of structural defects associated with the prenatal effects of alcohol as well as to establish a neurobehavioral phenotype. Appreciation of both of these issues is necessary to understand the full impact of alcohol on fetal development.

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Exploring behavioral phenotypes in a mouse model of fetal alcohol spectrum disorders

Chaudoin

Bonasera

Dunaevsky

et al. 2023

Developmental Neurobiology

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Fetal alcohol spectrum disorders are one of the leading causes of developmental abnormalities worldwide. Maternal consumption of alcohol during pregnancy leads to a diverse range of cognitive and neurobehavioral deficits. Although moderate‐to‐heavy levels of prenatal alcohol exposure (PAE) have been associated with adverse offspring outcomes, there is limited data on the consequences of chronic low‐level PAE. Here, we use a model of maternal voluntary alcohol consumption throughout gestation in a mouse model to investigate the effects of PAE on behavioral phenotypes during late adolescence and early adulthood in male and female offspring. Body composition was measured by dual‐energy X‐ray absorptiometry. Baseline behaviors, including feeding, drinking, and movement, were examined by performing home cage monitoring studies. The impact of PAE on motor function, motor skill learning, hyperactivity, acoustic reactivity, and sensorimotor gating was investigated by performing a battery of behavioral tests. PAE was found to be associated with altered body composition. No differences in overall movement, food, or water consumption were observed between control and PAE mice. Although PAE offspring of both sexes exhibited deficits in motor skill learning, no differences were observed in basic motor skills such as grip strength and motor coordination. PAE females exhibited a hyperactive phenotype in a novel environment. PAE mice exhibited increased reactivity to acoustic stimuli, and PAE females showed disrupted short‐term habituation. Sensorimotor gating was not altered in PAE mice. Collectively, our data show that chronic low‐level exposure to alcohol in utero results in behavioral impairments.

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Postnatal growth restriction and gene expression changes in a mouse model of fetal alcohol syndrome

Cited by 37 publications

References 54 publications

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

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

The effects of alcohol on fetal development

Exploring behavioral phenotypes in a mouse model of fetal alcohol spectrum disorders

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