Differential Transcript Usage in the Placenta is associated with in utero Arsenic Exposure and Fetal Growth Restriction
Year: 2019
Type: conference-abstract
Abstract: OPS 39: Metals and biomarkers, Room 411, Floor 4, August 26, 2019, 1:30 PM - 3:00 PM Background/Aim: Intrauterine arsenic and cadmium exposures have been linked with reduced birth weight as well as alterations in placental molecular features. However, studies thus far have focused on summarizing transcriptional activity at the gene level and do not capture isoform specification, a major driver in development that enables adaptive responses to the rapidly changing physiological conditions experienced early in life. In this study, we conducted a genome-wide analysis of the placental transcriptome to evaluate the role of isoform specification as a potential mediator in the pathway between intrauterine arsenic/cadmium exposure and fetal growth restriction. Methods: Transcriptome-wide RNA sequencing was performed in placenta samples from the Rhode Island Child Health Study (RICHS, n=200). Arsenic and cadmium levels were measured in maternal toe nails using ICP-MS. Differential transcript usage (DTU) between small (SGA) and appropriate (AGA) for gestational age infants was assessed using the DRIMSeq R package. Generalized linear models were assessed to determine the association between placental transcript proportions and arsenic/cadmium levels. Results: We identified 223 genes demonstrating SGA associated DTU (FDR<0.05). Among these, only 5 genes (SCAP, INHA, HNRNPA1, RAC1, CSNK1E) demonstrated differential expression at both the gene and transcript level. The transcript proportion of one SGA-DTU gene, TUSC3, was associated with intrauterine arsenic exposure (FDR<0.05). No differences were observed in association with intrauterine cadmium exposure. Discussion: We report the first genome-wide characterization of placental transcript usage and associations with intrauterine metal exposure and fetal growth restriction. Despite no difference in overall TUSC3 gene expression levels, both arsenic exposure and SGA status were associated with the expression of a specific TUSC3 transcript, suggesting a pathway by which an intrauterine exposure impacts fetal growth through perturbations of placental processes. These results highlight the utility of interrogating the transcriptome at deeper transcript-level resolution to identify novel placental biomarkers of exposure-induced outcomes.
Source: Environmental Epidemiology
Authors: Deyssenroth M, Peng S, Hao K, Jackson B, Marsit C, Chen J
Institutions: Icahn School of Medicine at Mount Sinai, Dartmouth College
Language: English
Subfield: Health, Toxicology and Mutagenesis
Field: Environmental Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $1,200
OpenAlex ID: W2981938762