ArticleCell death & disease2019
Di-n-butyl phthalate epigenetically induces reproductive toxicity via the PTEN/AKT pathway.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 40 citations in OpenAlex.
- Dysregulation of microRNA (miRNA) Due to Phthalate/Phthalate Metabolite Exposure and Associated Health Effects: A Narrative Review.Journal of xenobiotics · 2025Review
- Gossypol Acetic Acid Alleviates the Ferroptosis of Chondrocytes in Osteoarthritis by Inhibiting GPX4 Methylation.Current medicinal chemistry · 2025Article
- Phthalates and epigenetics: An emerging public health concern.Current research in toxicology · 2025Review
- Astragalus polysaccharides protect against Di-n-butyl phthalate-induced testicular damage by modulating oxidative stress, apoptosis, and the PI3K/Akt/mTOR pathway in rats.Frontiers in veterinary science · 2025Article
- Extracellular Vesicles in Environmental Toxicological Studies: Association between Urinary Concentrations of Phthalate Metabolites and Exosomal miRNA Expression Profiles.International journal of molecular sciences · 2024Article
- Elucidating the mechanisms and mitigation strategies for six-phthalate-induced toxicity in male germ cells.Frontiers in cell and developmental biology · 2024Article
- Lentinan induces apoptosis of mouse hepatocellular carcinoma cells through the EGR1/PTEN/AKT signaling axis.Oncology reports · 2023Article
- A Network Pharmacology-Based Study on the Mechanism of Dibutyl Phthalate ofBioMed research international · 2022Article
- LINC00511 promotes gastric cancer progression by regulating SOX4 and epigenetically repressing PTEN to activate PI3K/AKT pathway.Journal of cellular and molecular medicine · 2021Article
- Mechanistic insight into toxicity of phthalates, the involved receptors, and the role of Nrf2, NF-κB, and PI3K/AKT signaling pathways.Environmental science and pollution research international · 2021Review
- Article
- Cross Sectional Study on Exposure to BPA and Phthalates and Semen Parameters in Men Attending a Fertility Center.International journal of environmental research and public health · 2020Article
- Research Progress of Male Reproductive Toxicity of Chinese Materia Medicas.Evidence-based complementary and alternative medicine : eCAM · 2019Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Di-n-butyl phthalate (DBP) is a kind of ubiquitous chemical linked to hormonal disruptions that affects male reproductive system. However, the mechanism of DBP-induced germ cells toxicity remains unclear. Here, we demonstrate that DBP induces reduction of proliferation, increase of apoptosis and DNA damage dependent on the PTEN/AKT pathway. Mechanistically, DBP decreases PTEN promoter methylation and increases its transcriptional activity, leading to increased PTEN expression. Notably, DNMT3b is confirmed as a target of miR-29b and miR-29b-mediated status of PTEN methylation is involved in the effects of DBP treatment. Meanwhile, DBP decreases AKT pathway expression via increasing PTEN expression. In addition, the fact that DBP decreases the sperm number and the percentage of motile and progressive sperm is associated with downregulated AKT pathway and sperm flagellum-related genes. Collectively, these findings indicate that DBP induces aberrant PTEN demethylation, leading to inhibition of the AKT pathway, which contributes to the reproductive toxicity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.