Prenatal alcohol exposure is associated with changes in placental gene co-expression networks

Abstract

Alcohol consumption during pregnancy can result in a range of adverse postnatal outcomes among exposed children. However, identifying at-risk children is challenging given the difficulty to confirm prenatal alcohol exposure and the lack of early diagnostic tools. Placental surveys present an important opportunity to uncover early biomarkers to identify those at risk. Here, we report the first transcriptome-wide evaluation to comprehensively evaluate human placental pathways altered by fetal alcohol exposure. In a prospective longitudinal birth cohort in Cape Town, South Africa, we performed bulk tissue RNAseq in placenta samples from 32 women reporting heavy drinking during pregnancy and 30 abstainers/light drinkers. Weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis were performed to assess associations between fetal alcohol exposure and placental gene expression patterns at a network-wide and single gene level, respectively. The results revealed altered expression in genes related to erythropoiesis and angiogenesis, which are implicated in established postnatal phenotypes related to alcohol exposure, including disruptions in iron homeostasis, growth, and neurodevelopment. The reported findings provide insights into the molecular pathways affected by prenatal alcohol exposure and highlight the potential of placental biomarkers for detecting and understanding the effects of alcohol on fetal development.

Sex-Specific DNA Methylation and Gene Expression Changes in Mouse Placentas After Early Preimplantation Alcohol Exposure

“…Our findings highlight the value of exploring placental molecular pathways in the context of FASD. DMRs and DEGs in our model showed alterations with genes recently identified as deregulated in the placentas of women who engaged in heavy drinking during pregnancy, including the crucial 3week period around conception (Deyssenroth et al, 2024). The variations in alcohol exposure paradigms (single vs. multiple exposures), the influence of additional factors such as smoking (Hoch et al, 2023), sex-specific analyses, differences in exposure timing (pre-implantation vs. variable developmental time points), and species-specific differences may account for the limited overlap between our study and that of Deyssenroth et al Nonetheless, these observations underscore the relevance of our approach and its potential for furthering understanding in this field.…”

“…Interestingly, 1 genic male-DMRs (Rapgef2) and 5 genic female-DMRs (Hrh2, Kmt2a, Large1, Serpine1, Trim58) were associated with genes differentially expressed (n=40) in the placentas of women who reported heavy drinking during pregnancy (Deyssenroth et al, 2024). Among these, Rapgef2, involved in calcium ion binding and signal transducer activity, has been associated with cognitive impairment (Jang et al, 2021).…”

“…Notably, we identified 4 genes (Bahcc1, Bhlhe41, Prkd3, Slc4a1) with differential expression in the male EtOH-placenta and 2 genes (Bhlhe41, Slc9a8) with differential expression in female EtOHplacenta. These genes were among the 40 that were also dysregulated in the placentas of women who reported heavy drinking during pregnancy (Deyssenroth et al, 2024). Amid these, Bahcc1, involved in chromatin binding, is linked to KBG syndrome, which is characterized by distinctive craniofacial features, developmental delay, and intellectual disability.…”

“…Placental abnormalities lead to a range of adverse pregnancy outcomes, including embryonic growth delays, intrauterine growth restriction, preeclampsia, and preterm birth (Coussons-Read, 2013;Wadhwa et al, 2011). Interestingly, a recent study has revealed that prenatal alcohol exposure is linked to alterations in human placental gene expression (Deyssenroth et al, 2024). This underscores the potential role of this tissue in exploring and understanding the repercussions of alcohol on embryonic development.…”