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Biology subjects

Muggli, E.

Publications and source records attributed to Muggli, E..

3 recordsLinked to original sources

The influence of prenatal alcohol exposure and maternal diet on offspring DNA methylation: a cross-species study

Alcohol consumption in pregnancy can affect genome regulation in the developing offspring but results have been contradictory. We employed a physiologically relevant murine model of short-term moderate prenatal alcohol exposure (PAE) resembling common patterns of alcohol consumption in pregnancy in humans. Early moderate PAE was sufficient to affect site-specific DNA methylation in new-born pups without altering behavioural outcomes in adult littermates. Whole-genome bisulfite sequencing of neonatal brain and liver revealed stochastic influence on DNA methylation that was mostly tissue-specific, with some perturbations likely originating as early as gastrulation. DNA methylation differences were enriched in non-coding genomic regions with regulatory potential indicative of broad effects of alcohol on genome regulation. Replication studies in human cohorts with fetal alcohol spectrum disorder suggested some effects were metastable at genes linked to disease-relevant traits including facial morphology, intelligence, educational attainment, autism, and schizophrenia. In our murine model, a maternal diet high in folate and choline protected against some of the damaging effects of early moderate PAE on DNA methylation. Our studies demonstrate that early moderate exposure is sufficient to affect fetal genome regulation even in the absence of overt phenotypic changes and highlight a role for preventative maternal dietary interventions.

genetics↗

Pregnant womens understanding and conceptualisations of the harms from drinking alcohol: a qualitative study

BackgroundDespite womens awareness that drinking alcohol in pregnancy can lead to lifelong disabilities in a child, it appears that an awareness alone does not discourage some pregnant women from drinking. ObjectivesTo explore influences on pregnant womens decision making around alcohol use in a population with frequent and heavy peer drinking (i.e. in two Indigenous Australian communities) and another of non-Indigenous pregnant women attending antenatal care in a range of socioeconomic settings. MethodsIndividual and group discussions were held with both Indigenous Australian and non-Indigenous pregnant women attending a variety of antenatal care models, including two Indigenous maternity services in Australia. Data were analysed using inductive content analysis. ResultsA total of 14 Indigenous Australian and 14 non-Indigenous pregnant women participated in this study. Analysis identified five main influences on pregnant womens alcohol use: the level and detail of womens understanding of harm; womens information sources on alcohol use in pregnancy; how this information influenced their choices; how women conceptualised their pregnancy; and whether the social and cultural environment supported abstinence. Conclusions for practiceThis study provides insight into how Indigenous Australian and non-Indigenous pregnant women understand and conceptualise the harms from drinking alcohol, including how their social and cultural environments impact their ability to abstain. Strategies for behaviour change need to: correct misinformation about supposed safe timing, quantity and types of alcohol; develop a more accurate perception of Fetal Alcohol Spectrum Disorder; reframe messages about harm to messages about optimising the childs health and cognitive outcomes; and develop a holistic approach encompassing womens social and cultural context.

scientific communication and education↗

Placental DNA methylation signatures of maternal smoking during pregnancy and potential impacts on fetal growth

Maternal smoking during pregnancy (MSDP) contributes to poor birth outcomes, in part through disrupted placental functions, which may be reflected in the placental epigenome. We meta-analyzed the associations between MSDP and placental DNA methylation (DNAm) and between DNAm and birth outcomes within the Pregnancy And Childhood Epigenetics (PACE) consortium (7 studies, N=1700, 344 with any MSDP). We identified 1224 CpGs that were associated with MSDP, of which 341 associated with birth outcomes and 141 associated with gene expression. Only 6 of these CpGs were consistent with the findings from a prior meta-analysis of cord blood DNAm, demonstrating substantial tissue-specific responses to MSDP. The placental MSDP associated CpGs were enriched for growth-factor signaling, hormone activity, inflammation, and vascularization, which play important roles in placental function. We demonstrate links between placental DNAm, MSDP and poor birth outcomes, which may better inform the mechanisms through which MSDP impacts placental function and fetal growth.

genomics↗