학술논문
Mono(2-ethylhexyl) phthalate induces transcriptomic changes in placental cells based on concentration, fetal sex, and trophoblast cell type.
Document Type
Academic Journal
Author
Lapehn S; Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, 1900 9th Ave, Jack R. MacDonald Building, Seattle, WA, 98101, USA.; Houghtaling S; Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, 1900 9th Ave, Jack R. MacDonald Building, Seattle, WA, 98101, USA.; Ahuna K; Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, 97239, USA.; Kadam L; Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, 97239, USA.; MacDonald JW; Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, 98195, USA.; Bammler TK; Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, 98195, USA.; LeWinn KZ; Department of Psychiatry, University of California-San Francisco, San Francisco, CA, 94143, USA.; Myatt L; Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, 97239, USA.; Sathyanarayana S; Department of Pediatrics, University of Washington, Seattle, WA, 98195, USA.; Center for Child Health, Behavior and Development, Seattle Children's Research Institute, Seattle, WA, 98101, USA.; Paquette AG; Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, 1900 9th Ave, Jack R. MacDonald Building, Seattle, WA, 98101, USA. alison.paquette@seattlechildrens.org.; Department of Pediatrics, University of Washington, Seattle, WA, 98195, USA. alison.paquette@seattlechildrens.org.
Source
Publisher: Springer-Verlag Country of Publication: Germany NLM ID: 0417615 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-0738 (Electronic) Linking ISSN: 03405761 NLM ISO Abbreviation: Arch Toxicol Subsets: MEDLINE
Subject
Language
English
Abstract
Phthalates are ubiquitous plasticizer chemicals found in consumer products. Exposure to phthalates during pregnancy has been associated with adverse pregnancy and birth outcomes and differences in placental gene expression in human studies. The objective of this research was to evaluate global changes in placental gene expression via RNA sequencing in two placental cell models following exposure to the phthalate metabolite mono(2-ethylhexyl) phthalate (MEHP). HTR-8/SVneo and primary syncytiotrophoblast cells were exposed to three concentrations (1, 90, 180 µM) of MEHP for 24 h with DMSO (0.1%) as a vehicle control. mRNA and lncRNAs were quantified using paired-end RNA sequencing, followed by identification of differentially expressed genes (DEGs), significant KEGG pathways, and enriched transcription factors (TFs). MEHP caused gene expression changes across all concentrations for HTR-8/SVneo and primary syncytiotrophoblast cells. Sex-stratified analysis of primary cells identified different patterns of sensitivity in response to MEHP dose by sex, with male placentas being more responsive to MEHP exposure. Pathway analysis identified 11 KEGG pathways significantly associated with at least one concentration in both cell types. Four ligand-inducible nuclear hormone TFs (PPARG, PPARD, ESR1, AR) were enriched in at least three treatment groups. Overall, we demonstrated that MEHP differentially affects placental gene expression based on concentration, fetal sex, and trophoblast cell type. This study confirms prior studies, as enrichment of nuclear hormone receptor TFs were concordant with previously published mechanisms of phthalate disruption, and generates new hypotheses, as we identified many pathways and genes not previously linked to phthalate exposure.
(© 2023. The Author(s).)
(© 2023. The Author(s).)