ArticleBMC medicine2022
Chromatin modifier developmental pluripotency associated factor 4 (DPPA4) is a candidate gene for alcohol-induced developmental disorders.
Article in BMC medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Maternal smoking, consumption of alcohol, and caffeinated beverages during pregnancy and the risk of childhood brain tumors: a meta-analysis of observational studies.BMC public health · 2024Pooled it
- Dysmorphological and Neuropsychological Phenotypes of Prenatally Alcohol-Exposed 6-Year-Old Children: A Prospective Longitudinal Birth Cohort Study.Alcohol, clinical & experimental research · 2026Article
- Early biomarkers associated with prenatal alcohol exposure and neurodevelopmental outcomes.Frontiers in pharmacology · 2026Review
- Stem Cell Models for Elucidating Cellular Mechanisms of Substance Use Disorders and Advancing Addiction Pharmacology.Stem cells international · 2026Review
- Retrotransposon methylation profiles and survival in Black women with high-grade serous ovarian carcinoma.Clinical epigenetics · 2025Article
- Effects of alcohol on the transcriptome, methylome and metabolome of in vitro gastrulating human embryonic cells.Disease models & mechanisms · 2025Article
- Developmental pluripotency-associated 4 increases aggressiveness of pituitary neuroendocrine tumors by enhancing cell stemness.Neuro-oncology · 2025Article
- Nonconceptus Mechanisms of Prenatal Alcohol Exposure That Disrupt Embryo-Fetal Development: An Integrative View.Alcohol research : current reviews · 2025Review
- Genome-wide DNA methylation and gene expression in human placentas derived from assisted reproductive technology.Communications medicine · 2024Article
- FOXP2 overexpression upregulates LAMA4 expression and thereby alleviates preeclampsia by regulating trophoblast behavior.Communications biology · 2024Article
- The Impact of Oxidative Stress on the Epigenetics of Fetal Alcohol Spectrum Disorders.Antioxidants (Basel, Switzerland) · 2024Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundPrenatal alcohol exposure (PAE) affects embryonic development, causing a variable fetal alcohol spectrum disorder (FASD) phenotype with neuronal disorders and birth defects. We hypothesize that early alcohol-induced epigenetic changes disrupt the accurate developmental programming of embryo and consequently cause the complex phenotype of developmental disorders. To explore the etiology of FASD, we collected unique biological samples of 80 severely alcohol-exposed and 100 control newborns at birth.
methodsWe performed genome-wide DNA methylation (DNAm) and gene expression analyses of placentas by using microarrays (EPIC, Illumina) and mRNA sequencing, respectively. To test the manifestation of observed PAE-associated DNAm changes in embryonic tissues as well as potential biomarkers for PAE, we examined if the changes can be detected also in white blood cells or buccal epithelial cells of the same newborns by EpiTYPER. To explore the early effects of alcohol on extraembryonic placental tissue, we selected 27 newborns whose mothers had consumed alcohol up to gestational week 7 at maximum to the separate analyses. Furthermore, to explore the effects of early alcohol exposure on embryonic cells, human embryonic stem cells (hESCs) as well as hESCs during differentiation into endodermal, mesodermal, and ectodermal cells were exposed to alcohol in vitro.
resultsDPPA4, FOXP2, and TACR3 with significantly decreased DNAm were discovered-particularly the regulatory region of DPPA4 in the early alcohol-exposed placentas. When hESCs were exposed to alcohol in vitro, significantly altered regulation of DPPA2, a closely linked heterodimer of DPPA4, was observed. While the regulatory region of DPPA4 was unmethylated in both control and alcohol-exposed hESCs, alcohol-induced decreased DNAm similar to placenta was seen in in vitro differentiated mesodermal and ectodermal cells. Furthermore, common genes with alcohol-associated DNAm changes in placenta and hESCs were linked exclusively to the neurodevelopmental pathways in the enrichment analysis, which emphasizes the value of placental tissue when analyzing the effects of prenatal environment on human development.
conclusionsOur study shows the effects of early alcohol exposure on human embryonic and extraembryonic cells, introduces candidate genes for alcohol-induced developmental disorders, and reveals potential biomarkers for prenatal alcohol exposure.
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