Genome-wide DNA methylation study in human placenta identifies novel loci associated with maternal smoking during pregnancy

Morales, Eva; Vilahur, Nadia; Salas, Lucas A.; Motta, Valeria; Fernández, Mariana F.; Murcia, Mario; Llop, Sabrina; Tardón, Adonina; Fernández‐Tardón, Guillermo; Santa‐Marina, Loreto; Gallastegui, Mara; Bollati, Valentina; Estivill, Xavier; Olea, Nicolás; Sunyer, Jordi; Bustamante, Mariona

doi:10.1093/ije/dyw196

Cited by 77 publications

(67 citation statements)

References 40 publications

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“…Placental methylome may act as a functional record of in utero exposures; however, only few small studies have assessed the effect of maternal smoking during pregnancy on DNA methylation patterns in human placenta. We identified novel loci related to foetal growth that were differentially methylated in placenta in relation to maternal smoking during pregnancy which did not overlap with previous findings in cord blood …”

Section: What Are the Potential Mechanisms Underlying The Effects Of supporting

confidence: 46%

“…We identified novel loci related to foetal growth that were differentially methylated in placenta in relation to maternal smoking during pregnancy which did not overlap with previous findings in cord blood. 53 Overall (Figure 1), there is preliminary evidence of the important role of placenta in the pathways to brain development. Particulate matter (PM) could be related with mental development though impairing placental function, restricting foetal growth and inducting placental as well as systemic inflammation and oxidative stress.…”

Section: Mechanisms Underlying the Effects Of Air Pollution On Foetalmentioning

confidence: 96%

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Pre‐natal brain development as a target for urban air pollution

Sunyer

Dadvand

2019

Basic Clin Pharma Tox

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Air pollution is the main urban‐related environmental hazard and one of the major contributors to the global burden of disease based on its cardiovascular‐respiratory impacts. In children, exposure to urban air pollution is associated, among others, with decelerated neurodevelopment early in life and increased risk of neurodevelopmental problems such as attention‐deficit hyperactivity disorder, autism spectrum disorders, academic failure and the start of Alzheimer's pathogenesis. However, the evidence of the effects of air pollution on brain development is still inadequate, mainly due to the limitations in (a) characterizing brain development (most studies were based on subjective tools such as questionnaires or neuropsychological tests) and (b) air pollution exposure (most studies only used residential levels based on geographical modelling and also overlooking the variation in the mixture of air pollutants as well as the composition and hence toxicity of particulate pollutants in different settings), (c) the lack of studies during the most vulnerable stages of brain development (foetal and early life (first two years post‐natally)) and (d) the lack of structural and functional imaging data underlying these effects. In mice, in utero exposure to fine particles was linked to structural brain changes and there is a need to establish the generalizability of these findings in human beings. Though scarce, current evidence in children supports the importance of the pre‐natal period as a susceptible window of exposure. Two studies in schoolchildren found that pre‐natal air pollution exposure might damage brain structure while exposure during childhood was not linked to any structural alteration. Another study showed that children with higher traffic‐related air pollution at school had lower functional integration in key brain networks, but no changes in brain structure, possibly partly because of the time window of air pollution exposure (in utero versus childhood exposure). A key development is to discover the windows of greatest sensitivity of structural brain changes to air pollution exposure by incorporating the recent advances in non‐invasive imaging to characterize natal and post‐natal brain development and exploring whether and to what extend placental dysfunction could mediate such an association. Studying pre‐natal life is important because effects at this time are of a potentially irreversible nature and because the largest preventive opportunities occur during these periods.

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Section: What Are the Potential Mechanisms Underlying The Effects Of supporting

confidence: 46%

Section: Mechanisms Underlying the Effects Of Air Pollution On Foetalmentioning

confidence: 96%

Pre‐natal brain development as a target for urban air pollution

Sunyer

Dadvand

2019

Basic Clin Pharma Tox

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“…The MSDP-associated loci with the most statistically significant association (cg27402634), also identified in prior smoking EWAS of placental tissues 15 , yielded dramatically lower DNAm levels in association with MSDP exposure. This effect-size is much larger in magnitude (∼25% difference for sustained MSDP) compared to what has generally been observed in most exposure-focused EWAS, though within the same range as a CpG site in AHRR (cg05575921; 18% difference between exposed and unexposed) from a prior EWAS of current smoking and blood DNAm 34 .…”

Section: Discussionmentioning

confidence: 67%

“…However, the placental epigenome has not been as thoroughly studied, though the placenta is likely a critical target organ of MSDP-associated toxicity. A handful of prior studies have examined the relationships between MSDP and (DNAm) in human placenta 11–14 , identifying MSDP-associated loci some of which have been suggested partially mediate the effects of MSDP on lower birth weight 15 .…”

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confidence: 99%

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

Everson

Vives-Usano

Seyve

et al. 2019

Preprint

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“…29,59 Outros estudos também demostraram uma associação entre o tabagismo materno durante a gestação e a metilação do DNA. [60][61][62][63] No entanto, estudos anteriores que evidenciaram a associação entre o início da AIJ e a exposição ao tabaco durante a gravidez permanecem controversos. [41][42][43]64 Diferentemente de nossos achados, Shenoi e cols., em dois estudos casocontroles, publicados recentemente, não evidenciaram associação entre AIJ e tabagismo materno durante a gestação.…”

Section: Resultados Da Exposição De Pacientes Com Aij Sistêmica E Outunclassified

Avaliação da influência de fatores ambientais sobre o diagnóstico de artrite idiopática juvenil em crianças e adolescentes

França¹

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À Deus, que sempre me mostrou os melhores caminhos a trilhar, providenciando soluções quando necessário, e por nunca me deixar desistir frente às dificuldades.À minha mãe, Lumena, minha melhor amiga, meu exemplo de força, generosidade e perseverança, e ao meu pai, Mário, minha gratidão pelo amor, incentivo e apoio desmedidos.Ao meu esposo, Patrick, que esteve sempre ao meu lado nas conquistas e nas horas difíceis, acreditando em meu potencial e fornecendo todo o apoio necessário para atingir meus objetivos.À minha orientadora, Dra Sylvia Farhat, uma grata surpresa, que se mostrou uma grande amiga: sensível, compreensiva, solícita, humilde, detentora de um conhecimento teórico admirável e um instinto maternal imensurável. Minha eterna gratidão e admiração! Ao meu chefe e amigo Dr Clóvis, exemplo de entusiasmo pela pesquisa, grande incentivador para a realização desse trabalho, professor incomparável, chefe agregador e acolhedor, responsável por muitas horas de estudo, pela elevação da minha autoestima, pela confiança e por muitos momentos felizes vividos no Instituto da Criança.À minha coorientadora, Dra Adriana Sallum, e às demais assistentes da Reumatologia Pediátrica do ICr, Dras Lúcia Campos, Nadia Aikawa e Kátia Kozu, pela amizade sincera, torcida, palavras de apoio, confiança e orientação na vida pessoal e profissional.Aos meus amigos e companheiros de todas as horas na Reumatologia Pediátrica, Maria Fernanda, Izabel, Victor, Roberta, Marco Felipe, Erica, Daniela, Gabriela, Andressa e Natali. Obrigada por tornarem os momentos difíceis longe de casa mais fáceis e leves, pelas divisões de trabalho e de experiências e pelos ombros amigos! Às minhas irmãs, Natália e Débora, à minha sobrinha, Amanda, às minhas tias, Vera Lúcia (in memória), Verônica, Rosa, Socorro, ao meu tio Alberto, e à minha sogra, Graça, pela torcida, pelas orações e por todo o apoio dado para que esse doutorado se realizasse.Às minhas amigas tão presentes, Lívia Timbó e Larissa Bezerra que, em especial, me apoiaram longe da minha família e me ajudaram muito com os controles, sendo essenciais para a realização deste trabalho.Aos meus amigos de faculdade, Julianne, Fernanda, Bruno, Rita, Carolina, Matheus, Rosa e Daniela, companheiros de longa jornada, exemplos de médicos honestos e humanos, amigos fiéis e grandes incentivadores das conquistas profissionais.Aos colegas de plantão, que me ajudaram muito a conseguir controles saudáveis para a pesquisa.Aos pacientes e familiares, que tornaram possível este estudo. Esta tese está de acordo com as seguintes normas, em vigor no momento desta publicação:Referências: adaptado de International Committee of Medical Journals Editors (Vancouver).

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Genome-wide DNA methylation study in human placenta identifies novel loci associated with maternal smoking during pregnancy

Abstract: We identified novel loci differentially methylated in placenta in relation to maternal smoking during pregnancy. Adverse effects of maternal smoking on birthweight of the offspring may be mediated by alterations in the placental methylome.

Cited by 77 publications

References 40 publications

Pre‐natal brain development as a target for urban air pollution

Pre‐natal brain development as a target for urban air pollution

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

Avaliação da influência de fatores ambientais sobre o diagnóstico de artrite idiopática juvenil em crianças e adolescentes

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