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Genetics

Poster Session 4

(1181) Maternal and fetal tissue specific response to phthalate exposure in the third trimester

Wednesday, February 14, 2024
1:00 PM – 2:30 PM  
Location: Prince George's Exhibit Hall CDE, Lower Atrium Level
Objective: Exposure to phthalates, a class of endocrine disruptors, is pervasive in the modern environment. Exposure during pregnancy has been associated with outcomes like preterm birth, gestational diabetes, and preeclampsia. We hypothesized that high exposure levels will yield specific responses in maternal and fetal tissues.

Study Design: Using matched urine and plasma samples collected in 57 singleton women (median 25 weeks gestation), the concentrations of 17 urinary phthalate metabolites were measured using quantitative mass spectrometry, and maternal cell free RNA was characterized via RNA sequencing. Samples above and below the median for each metabolite were considered high and low exposure, respectively. The fgsea package from Bioconductor was used for gene set enrichment analysis. The cell type signature gene set collection (C8 v2023.1.Hs) from the Molecular Signatures Database was used to identify affected maternal and fetal tissues. Normalized enrichment scores (NES) were compared by high vs low exposure level for each phthalate metabolite. P-values adjusted for multiple testing. 

Results:

The heat maps displayed NES significance at an adjusted p-value < 0.01 for tissue-specific gene sets by phthalate metabolite. Tissues with altered NES in both maternal and fetal tissues included pancreas, brain, gastrointestinal, kidney, liver, lung, eye. Among fetal gene sets, adrenal, blood, heart, immune, lymphatic, muscle, placental, splenic, stomach, thymic, and vascular showed altered NES. Among maternal gene sets bone marrow, olfactory, ovary, and skeletal muscle showed altered NES. Affected tissues were primarily endocrine and high metabolizing tissues.

Conclusion:

This novel analysis of gene set expression in response to high vs. low phthalate exposure during the early third trimester demonstrated both up and down regulation in gene expression across a wide variety of fetal and maternal tissues. The patterns of gene set alteration differed between the maternal and fetal context and may suggest potential mechanisms that underly observed associations between phthalate exposure and pregnancy outcomes.