ArticleEnvironmental health perspectives2019
The Role of Peroxisome Proliferator–Activated Receptor Gamma (PPARγ) in Mono(2-ethylhexyl) Phthalate (MEHP)-Mediated Cytotrophoblast Differentiation.
Article in Environmental health perspectives, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 78 citations in OpenAlex.
- Review
- Mono(2-Ethylhexyl) Phthalate Induces Inflammatory and Angiogenic Alterations Mediated by the PI3K/AKT Pathway in HTR-8/SVneo Trophoblastic Cells.Environmental toxicology · 2026Article
- Investigating Birth and Thyroid Outcomes of Maternal-Fetal Environmental Exposures (IBM-E): A Cohort Protocol for Dietary Iodine and Endocrine Disruptors.Endocrinology and metabolism (Seoul, Korea) · 2025Observational
- Cerium dioxide nanoparticles coated with benzo[a]pyrene modify aryl hydrocarbon receptor activity, trophoblast differentiation and mitochondrial network phenotype in human placenta.Particle and fibre toxicology · 2025Article
- Effect Modification of Serum Omega-3 Fatty Acids on the Associations between Urinary Phthalate Biomarkers Mixture and Pregnancy Outcomes among Women Seeking Fertility Care.Environmental health perspectives · 2025Article
- The anti-inflammatory effect of the amniotic PPARγ pathways is not dysregulated by the alternative plasticizer DINCH and its metabolite MINCH in human fetal membranes.Environmental science and pollution research international · 2025Article
- Review
- Individual and joint effects of phthalates exposure on the risk of early miscarriage.Journal of exposure science & environmental epidemiology · 2024Article
- Placental cell conditioned media modifies hematopoietic stem cell transcriptome invitro.Placenta · 2024Article
- Perfluorooctanoic acid induces transcriptomic alterations in second trimester human cytotrophoblasts.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Review
- Article
- IFITM1 inhibits trophoblast invasion and is induced in placentas associated with IFN-mediated pregnancy diseases.iScience · 2023Article
- Review
- Self-assembled human placental model from trophoblast stem cells in a dynamic organ-on-a-chip system.Cell proliferation · 2023Article
- Mono(2-ethylhexyl) phthalate induces transcriptomic changes in placental cells based on concentration, fetal sex, and trophoblast cell type.Archives of toxicology · 2023Article
- Regulators involved in trophoblast syncytialization in the placenta of intrauterine growth restriction.Frontiers in endocrinology · 2023Review
- Role of microRNA in Endocrine Disruptor-Induced Immunomodulation of Metabolic Health.Metabolites · 2022Review
- Maternal urinary phthalate metabolites are associated with lipidomic signatures among pregnant women in Puerto Rico.Journal of exposure science & environmental epidemiology · 2022Article
- Dysregulation of the Amniotic PPARγ Pathway by Phthalates: Modulation of the Anti-Inflammatory Activity of PPARγ in Human Fetal Membranes.Life (Basel, Switzerland) · 2022Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPhthalates are environmental contaminants commonly used as plasticizers in polyvinyl chloride (PVC) products. Recently, exposure to phthalates has been associated with preterm birth, low birth weight, and pregnancy loss. There is limited information about the possible mechanisms linking maternal phthalate exposure and placental development, but one such mechanism may be mediated by peroxisome proliferator–activated receptor γ (PPARγ). PPARγ belongs to the nuclear receptor superfamily that regulates, in a ligand-dependent manner, the transcription of target genes. Studies of PPARγ-deficient mice have demonstrated its essential role in lipid metabolism and placental development. In the human placenta, PPARγ is expressed in the villous cytotrophoblast (VCT) and is activated during its differentiation into syncytiotrophoblast.
objectivesThe goal of this study was to investigate the action of mono(2-ethylhexyl) phthalate (MEHP) on PPARγ activity during
methodsWe combined immunofluorescence, PPARγ activity/hCG assays, western blotting, and lipidomics analyses to characterize the impacts of physiologically relevant concentrations of MEHP (0.1, 1, and 10 μM) on cultured VCTs isolated from human term placentas.
resultsDoses of 0.1 and 1 μM MEHP showed significantly lower PPARγ activity and less VCT differentiation in comparison with controls, whereas, surprisingly, a 10 μM dose had the opposite effect. MEHP exposure inhibited hCG production and significantly altered lipid composition. In addition, MEHP had significant effects on the mitogen-activated protein kinase (MAPK) pathway.
conclusionsThis study suggests that MEHP has a U-shaped dose–response effect on trophoblast differentiation that is mediated by the PPARγ pathway and acts as an endocrine disruptor in the human placenta. https://doi.org/10.1289/EHP3730.
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