ArticleArchives of toxicology2019
Multispecies study: low-dose tributyltin impairs ovarian theca cell cholesterol homeostasis through the RXR pathway in five mammalian species including humans.
Article in Archives of toxicology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. 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, 24 citations in OpenAlex.
- Environmental and external stressors of postejaculatory sperm function.The Journal of reproduction and development · 2026Review
- Delineating lipidomic landscapes in human and mouse ovaries: Spatial signatures and chemically-induced alterations via MALDI mass spectrometry imaging: Spatial ovarian lipidomics.Environment international · 2024Article
- Reduced bioenergetics and mitochondrial fragmentation in human primary cytotrophoblasts induced by an EGFR-targeting chemical mixture.Chemosphere · 2024Article
- Review
- Evaluation of Lipids and Lipid-Related Transcripts in Human and Ovine Theca Cells and anEnvironmental health perspectives · 2024Article
- Organotin mixtures reveal interactions that modulate adipogenic differentiation in 3T3-L1 preadipocytes.Archives of toxicology · 2023Article
- Review
- Organotin Antifouling Compounds and Sex-Steroid Nuclear Receptor Perturbation: Some Structural Insights.Toxics · 2022Article
- The organotin triphenyltin disrupts cholesterol signaling in mammalian ovarian steroidogenic cells through a combination of LXR and RXR modulation.Toxicology and applied pharmacology · 2022Article
- Expression of ABC transporters during syncytialization in preeclampsia.Pregnancy hypertension · 2022Article
- A 3-dimensional microfluidic platform for modeling human extravillous trophoblast invasion and toxicological screening.Lab on a chip · 2021Article
- Bisphenol S and Epidermal Growth Factor Receptor Signaling in Human Placental Cytotrophoblasts.Environmental health perspectives · 2021Article
- The new kids on the block: Emerging obesogens.Advances in pharmacology (San Diego, Calif.) · 2021Review
- Bisphenol S enhances gap junction intercellular communication in ovarian theca cells.Chemosphere · 2021Article
- In Vitro Effects of Emerging Bisphenols on Myocyte Differentiation and Insulin Responsiveness.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- Mitochondrial Epigenetics and Environmental Health: Making a Case for Endocrine Disrupting Chemicals.Toxicological sciences : an official journal of the Society of Toxicology · 2020Review
- Gestational Exposure to Bisphenol A and Bisphenol S Leads to Fetal Skeletal Muscle Hypertrophy Independent of Sex.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Tributyltin (TBT), an organotin chemical used as a catalyst and biocide, can stimulate cholesterol efflux in non-steroidogenic cells. Since cholesterol is the first limiting step for sex hormone production, we hypothesized that TBT disrupts intracellular cholesterol transport and impairs steroidogenesis in ovarian theca cells. We investigated TBT's effect on cholesterol trafficking, luteinization, and steroidogenesis in theca cells of five species (human, sheep, cow, pig, and mice). Primary theca cells were exposed to an environmentally relevant dose of TBT (1 or 10 ng/ml) and/or retinoid X receptor (RXR) antagonist. The expression of RXRα in sheep theca cells was knocked down using shRNA. Steroidogenic enzymes, cholesterol transport factors, and nuclear receptors were measured by RT-qPCR and Western blotting, and intracellular cholesterol, progesterone, and testosterone secretion by ELISA. TBT upregulated StAR and ABCA1 in ovine cells, and SREBF1 mRNA in theca cells. TBT also reduced intracellular cholesterol and upregulated ABCA1 protein expression but did not alter testosterone or progesterone production. RXR antagonist and RXRα knockdown demonstrates that TBT's effect is partially through RXR. TBT's effect on ABCA1 and StAR expression was recapitulated in all five species. TBT, at an environmentally relevant dose, stimulates theca cell cholesterol extracellular efflux via the RXR pathway, triggers a compensatory upregulation of StAR that regulates cholesterol transfer into the mitochondria and SREBF1 for de novo cholesterol synthesis. Similar results were obtained in all five species evaluated (human, sheep, cow, pig, and mice) and are supportive of TBT's conserved mechanism of action across mammalian species.
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.