scholarly journals Pre-implantation alcohol exposure induces lasting sex-specific DNA methylation programming errors in the developing forebrain

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
L. M. Legault ◽  
K. Doiron ◽  
M. Breton-Larrivée ◽  
A. Langford-Avelar ◽  
A. Lemieux ◽  
...  

Abstract Background Prenatal alcohol exposure is recognized for altering DNA methylation profiles of brain cells during development, and to be part of the molecular basis underpinning Fetal Alcohol Spectrum Disorder (FASD) etiology.  However, we have negligible information on the effects of alcohol exposure during pre-implantation, the early embryonic window marked with dynamic DNA methylation reprogramming, and on how this may rewire the brain developmental program. Results Using a pre-clinical in vivo mouse model, we show that a binge-like alcohol exposure during pre-implantation at the 8-cell stage leads to surge in morphological brain defects and adverse developmental outcomes during fetal life. Genome-wide DNA methylation analyses of fetal forebrains uncovered sex-specific alterations, including partial loss of DNA methylation maintenance at imprinting control regions, and abnormal de novo DNA methylation profiles in various biological pathways (e.g., neural/brain development). Conclusion These findings support that alcohol-induced DNA methylation programming deviations during pre-implantation could contribute to the manifestation of neurodevelopmental phenotypes associated with FASD.

2020 ◽  
Author(s):  
LM Legault ◽  
K Doiron ◽  
M Breton-Larrivée ◽  
A Langford-Avelar ◽  
A Lemieux ◽  
...  

ABSTRACTPrenatal alcohol exposure is recognized for altering DNA methylation profiles of brain cells during development, and to be part of the molecular basis underpinning Fetal Alcohol Spectrum Disorder (FASD) etiology. However, we have negligible information on the effects of alcohol exposure during pre-implantation, the early embryonic window marked with dynamic DNA methylation reprogramming, and on how this may rewire the brain developmental program. Using a pre-clinical in vivo mouse model, we show that pre-implantation alcohol exposure leads to adverse developmental outcomes that replicate clinical characteristics observed in children with FASD. Genome-wide DNA methylation analyses of fetal forebrains uncovered sex-specific alterations, including partial loss of DNA methylation maintenance at imprinting control regions, and abnormal de novo DNA methylation profiles in various biological pathways (e.g., neural/brain development). These findings support the contribution of alcohol-induced DNA methylation programming deviations during pre-implantation to the manifestation of neurodevelopmental phenotypes associated with FASD.


Epigenomics ◽  
2021 ◽  
Author(s):  
Yuk Jing Loke ◽  
Evelyne Muggli ◽  
Richard Saffery ◽  
Joanne Ryan ◽  
Sharon Lewis ◽  
...  

Background: Binge level prenatal alcohol exposure (PAE) causes developmental abnormalities, which may be mediated in part by epigenetic mechanisms. Despite this, few studies have characterised the association of binge PAE with DNA methylation in offspring. Methods: We investigated the association between binge PAE and genome-wide DNA methylation profiles in a sex-specific manner in neonatal buccal and placental samples. Results: We identified no differentially methylated CpGs or differentially methylated regions (DMRs) at false discovery rate <0.05. However, using a sum-of-ranks approach, we identified a DMR in each tissue of female offspring. The DMR identified in buccal samples is located near regions with previously-reported associations to fetal alcohol spectrum disorder (FASD) and binge PAE. Conclusion: Our findings warrant further replication and highlight a potential epigenetic link between binge PAE and FASD.


2021 ◽  
Vol 45 (2) ◽  
pp. 155-172
Author(s):  
David J Gilbert ◽  
Raja AS Mukherjee ◽  
Nisha Kassam ◽  
Penny A Cook

Fetal alcohol spectrum disorder (FASD) is one outcome from prenatal alcohol exposure. Social workers are likely to encounter children with the condition, due to the greater likelihood of prenatal alcohol exposure among children in social services settings. This study explores the experiences of social workers in working with children suspected of having FASD and the support offered to social workers, the children and their families. Semi-structured interviews followed by qualitative framework analysis were conducted with seven child and family social workers along with one child protection solicitor who had experience of handling FASD cases. The two main themes that emerged from the data were a lack of knowledge about FASD and the paucity of diagnosis. Lack of knowledge among the social workers was linked to difficulty in managing children suspected to have the condition, feelings of frustration and normalisation of challenging behaviours. The paucity of diagnosis led to an under-emphasis of FASD in assessments, a dearth of specialist services and confusion about its specific effects in contexts of multiple substance misuse and harmful socio-environmental factors. The need for increased FASD awareness within social services and the development of FASD-targeted support for children and families is highlighted. Social workers would benefit from the inclusion of FASD-focused training in their curricula and professional development plans. Improving the diagnostic capacities of health institutions would address the paucity of diagnosis and raise the profile of FASD, especially in the social services setting.


2021 ◽  
pp. 070674372110532
Author(s):  
Katherine Flannigan ◽  
Carly McMorris ◽  
Amanda Ewasiuk ◽  
Dorothy Badry ◽  
Mansfield Mela ◽  
...  

Objective Individuals with fetal alcohol spectrum disorder (FASD) experience a range of complex neurodevelopmental, psychological, and socioenvironmental vulnerabilities. There is growing evidence that suicidal ideation, attempts, and death by suicide are significant concerns within this population. In this study, we (1) determined the rate of suicidal ideation/attempts in a large group of individuals with prenatal alcohol exposure (PAE) who were assessed for FASD in Canada and (2) investigated the associations between suicidal ideation/attempts and select demographic and biopsychosocial factors in this group. Method A secondary analysis of data from Canada's National FASD Database, a national repository of clinical information gathered through FASD assessment and diagnostic clinics across the country, was conducted. Descriptive analyses, chi-square/Fisher's exact tests, and binary logistic regression were used to examine demographic and biopsychosocial variables and their associations with suicidality. Results In our sample of 796 participants ( Mage = 17.7 years, range = 6–59; 57.6% male) assessed for FASD, 25.9% were reported to experience suicidal ideation/attempts. Numerous demographic and biopsychosocial factors were found to be significantly associated with suicidal ideation/attempts. The strongest associations with suicidal ideation/attempts were substance use, history of trauma/abuse, and impaired affect regulation. Conclusions With this study, we contribute to the emerging evidence of elevated risk of suicidality among individuals with PAE/FASD and improve our understanding of factors that may exacerbate this risk. Findings have relevance for improving screening, prevention, and proactive treatment approaches for individuals with PAE and FASD, their families, and wider support systems.


2013 ◽  
Vol 2 (3) ◽  
pp. 37-49 ◽  
Author(s):  
Therese M Grant ◽  
Natalie Novick Brown ◽  
J. Christopher Graham ◽  
Nancy Whitney ◽  
Dan Dubovsky ◽  
...  

Grant, T., Novick Brown, N., Graham, J., Whitney, N., Dubovsky, D. , & Nelson, L. (2013). Screening in treatment programs for Fetal Alcohol Spectrum Disorders that could affect therapeutic progress. The International Journal Of Alcohol And Drug Research, 2(3), 37-49. doi:10.7895/ijadr.v2i3.116 (http://dx.doi.org/10.7895/ijadr.v2i3.116)Aims: While structured intake interviews are the standard of care in substance abuse treatment programs, these interviews often do not screen for cognitive impairments, such as those found in fetal alcohol spectrum disorders (FASD) and other brain-based developmental disorders. The research reported here supports a brief interview protocol, the Life History Screen (LHS), that screens clients unobtrusively for adverse life-course outcomes typically found in FASD, so as to guide follow-up assessments and treatment planning.Design: Two-group observational study.Setting: A three-year case management intervention program in Washington State for high-risk women who abuse alcohol and/or drugs during pregnancy.Participants: Group 1: No prenatal alcohol exposure (N = 463); Group 2: Diagnosed with FASD (Fetal Alcohol Syndrome, Alcohol Related Neurodevelopmental Disorder, fetal alcohol effects, or static encephalopathy) by a qualified physician (N = 25), or suspected of having FASD (reported prenatal alcohol exposure and displayed behaviors consistent with a clinical diagnosis of FASD) (N = 61).Measures: The Addiction Severity Index (ASI) was administered to participants at intake. We analyzed eleven ASI items that corresponded to questions on the LHS in order to assess the potential of the LHS for identifying adults with possible FASD. The Life History Screen itself was not administered.Findings: Analysis of group differences between the diagnosed FASD and suspected FASD groups supported our decision to collapse the two groups for the main analysis. The Life History Screen shows promise as an efficient pre-treatment screen, in that core items are significantly associated with FASD group membership on factors involving childhood history, maternal drinking, education, substance use, employment, and psychiatric symptomatology.Conclusions: The Life History Screen may have utility as a self-report measure that can be used at the outset of treatment to identify clients with cognitive impairments and learning disabilities due to prenatal alcohol exposure.


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