ArticlePloS one2013
Cytochrome P450 3A1 mediates 2,2',4,4'-tetrabromodiphenyl ether-induced reduction of spermatogenesis in adult rats.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 54 citations in OpenAlex.
- CYP3A triggers BDE47-induced ferritinophagy and ferroptosis in spermatogenic cells through ROS-mediated mJournal of biomedical research · 2026Article
- Update of the risk assessment of polybrominated diphenyl ethers (PBDEs) in food.EFSA journal. European Food Safety Authority · 2024Article
- Toxic Effects and Mechanisms of Polybrominated Diphenyl Ethers.International journal of molecular sciences · 2023Review
- Reproductive toxicity of emerging plasticizers, flame retardants, and bisphenols, using culture of the rat fetal testis†.Biology of reproduction · 2023Article
- An Analysis of the Structural Relationship between Thyroid Hormone-Signaling Disruption and Polybrominated Diphenyl Ethers: Potential Implications for Male Infertility.International journal of molecular sciences · 2023Article
- Mechanisms of Male Reproductive Toxicity of Polybrominated Diphenyl Ethers.International journal of molecular sciences · 2022Review
- Characterization of 2,2',4,4'-tetrabromodiphenyl ether (BDE47)-induced testicular toxicity via single-cell RNA-sequencing.Precision clinical medicine · 2022Article
- Per- and polyfluoroalkyl mixtures toxicity assessment "Proof-of-Concept" illustration for the hazard index approach.Journal of toxicology and environmental health. Part A · 2021Article
- Integrated Proteomic and Metabolomic Analysis of the Testes Characterizes BDE-47-Induced Reproductive Toxicity in Mice.Biomolecules · 2021Article
- Epidermal growth factor regulates the development of stem and progenitor Leydig cells in rats.Journal of cellular and molecular medicine · 2020Article
- Propofol Inhibits Androgen Production in Rat Immature Leydig Cells.Frontiers in pharmacology · 2019Article
- Metabolomics coupled with pathway analysis characterizes metabolic changes in response to BDE-3 induced reproductive toxicity in mice.Scientific reports · 2018Article
- Interaction between β-hexachlorocyclohexane and ADIPOQ genotypes contributes to the risk of type 2 diabetes mellitus in East Chinese adults.Scientific reports · 2016Article
- BDE47 induces rat CYP3A1 by targeting the transcriptional regulation of miR-23b.Scientific reports · 2016Article
- Environmental exposure to BDE47 is associated with increased diabetes prevalence: Evidence from community-based case-control studies and an animal experiment.Scientific reports · 2016Article
- Characterization of the molecular degradation mechanism of diphenyl ethers by Cupriavidus sp. WS.Environmental science and pollution research international · 2015Article
- Differential nanoreprotoxicity of silver nanoparticles in male somatic cells and spermatogonial stem cells.International journal of nanomedicine · 2015Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background2,2',4,4'-tetrabromodiphenyl ether (BDE47) is the dominant PBDE congener in humans, wildlife, and the environment. It has been reported to be metabolized by cytochrome P450 (CYP) enzymes. Still, the effects of BDE47 on spermatogenesis failure are attracting an increasing amount of attention. However, it is unclear whether CYP-mediated metabolism contributes to BDE47-induced reproductive toxicity. METHODOLOGY AND PRINCIPAL
findingsThe role of cytochrome P450 3A1 (CYP3A1) in the formation of oxidative metabolites of BDE47 and its induced spermatogenesis failure was investigated in SD rats. BDE47 significantly increased the expression and activity of CYP3A1 in rat liver, and 3-OH-BDE47, the major oxidative metabolite of BDE47, dose-dependently increased in rat liver, serum, and testis, which was aggravated by dexamethasone (DEX), an inducer of CYP3A1. Additionally, testicular 3-OH-BDE47 and reactive oxygen species (ROS) in seminiferous tubules increased especially when BDE47 was administered in combination with DEX, which was confirmed in GC-1 and GC-2 cells that 3-OH-BDE47 induced more ROS production and cell apoptosis via the upregulation of FAS/FASL, p-p53 and caspase 3. As a result, daily sperm production dose-dependently decreased, consistent with histological observations in giant cells and vacuolar spaces and increase in TUNEL-positive apoptotic germ cells.
conclusionCYP3A1-mediated metabolic activation of BDE47 and the active metabolite 3-OH-BDE47 and consequent ROS played an important role in reduction of spermatogenesis by germ cell apoptosis. Our study helps provide new insights into the mechanism of reproductive toxicity of environmental chemicals.
Indexed as
Identifiers
What OpenQuestion holds
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 OpenQuestion graph.