ArticleToxicological sciences : an official journal of the Society of Toxicology2021
Dolutegravir Impairs Stem Cell-Based 3D Morphogenesis Models in a Manner Dependent on Dose and Timing of Exposure: An Implication for Its Developmental Toxicity.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 18 citations in OpenAlex.
- Developmental Toxicity Evaluation of the Dietary Supplement Vinpocetine Using Mouse and Human 3D Gastruloids.Birth defects research · 2026Article
- Embryotoxicity analysis of anti-arrhythmia drugs amiodarone, dronedarone, and their metabolites using 3D gastruloid models.Reproductive toxicology (Elmsford, N.Y.) · 2025Article
- Detection of developmental toxicity of the anti-COVID-19 drug molnupiravir using gastruloid-based in vitro assays.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- CEST MRI detects antiretroviral drug toxicities in the developing mouse brain.Frontiers in pharmacology · 2025Article
- Dolutegravir and Folic Acid Interaction during Neural System Development in Zebrafish Embryos.International journal of molecular sciences · 2024Article
- Dolutegravir induces FOLR1 expression during brain organoid development.Frontiers in molecular neuroscience · 2024Article
- Exposure to the antiretroviral drug dolutegravir impairs structure and neurogenesis in a forebrain organoid model of human embryonic cortical development.Frontiers in molecular neuroscience · 2024Article
- Metabolic implications and safety of dolutegravir use in pregnancy.The lancet. HIV · 2023Review
- Cabotegravir Exposure of Zebrafish (International journal of molecular sciences · 2023Article
- Developmental toxicity of remdesivir, an anti-COVID-19 drug, is implicated by in vitro assays using morphogenetic embryoid bodies of mouse and human pluripotent stem cells.Birth defects research · 2023Article
- Long-acting dolutegravir formulations prevent neurodevelopmental impairments in a mouse model.Frontiers in pharmacology · 2023Article
- Gene-nutrient interactions that impact magnesium homeostasis increase risk for neural tube defects in mice exposed to dolutegravir.Frontiers in cell and developmental biology · 2023Article
- HIV-1 Integrase Strand Transfer Inhibitors and Neurodevelopment.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Second-Generation Human Immunodeficiency Virus Integrase Inhibitors Induce Differentiation Dysregulation and Exert Toxic Effects in Human Embryonic Stem Cell and Mouse Models.The Journal of infectious diseases · 2022Article
- Gastruloids: Pluripotent stem cell models of mammalian gastrulation and embryo engineering.Developmental biology · 2022Article
- Using 2D and 3D pluripotent stem cell models to study neurotropic viruses.Frontiers in virology (Lausanne, Switzerland) · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Dolutegravir (DTG) is an antiretroviral drug of the integrase strand transfer inhibitor (INSTI) class used to treat human immunodeficiency virus infection. It is the recommended first-line regimen for most people, including women of childbearing age. However, some human and animal studies have suggested that DTG causes birth defects, although its developmental toxicity remains controversial. Here, we investigated the adverse effects of DTG using pluripotent stem cell-based in vitro morphogenesis models that have previously been validated as effective tools to assess the developmental toxicity of various chemicals. DTG diminished the growth and axial elongation of the morphogenesis model of mouse pluripotent stem cells at exposures of 2 μM and above in a concentration-dependent manner. Concomitantly, DTG altered the expression profiles of developmental regulator genes involved in embryonic patterning. The adverse effects were observed when the morphogenesis model was exposed to DTG at early stages of development, but not at later stages. The potency and molecular impact of DTG on the morphogenesis model were distinct from other INSTIs. Last, DTG altered the growth and gene expression profiles of the morphogenesis model of human embryonic stem cells at 1 μM and above. These studies demonstrate that DTG impairs morphological and molecular aspects of the in vitro morphogenesis models in a manner dependent on dose and timing of exposure through mechanisms that are unrelated to its action as an INSTI. This finding will be useful for interpreting the conflicting outcomes regarding the developmental toxicity of DTG in human and animal studies.
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.