Insights into cardiovascular development of zebrafish embryo after exposure to dolutegravir

Article Open access Published: 11 October 2026 Sara Ferretti 1 , Daniela Zizioli 1 , Matteo Manenti 2 , 3 , Giorgio Tiecco ORCID: orcid.org/0000-0002-7366-871X 2 , 3 , Eugenio Monti 1 , Francesco Castelli 2 , 3 , Eugenia Quiros-Roldan 2 , 3 & ... Isabella Zanella 1 , 4 Scientific Reports ( 2026 ) Cite this article We’re sharing this article early to provide faster access to peer-reviewed, accepted research.

It is citable and carries a permanent DOI. This version is subject to further edits and will be replaced automatically by the final Version of Record. All legal disclaimers apply.

Abstract The use of the up-to-date antiretroviral therapy (ART), including the integrase strand-transfer inhibitors (INSTIs), has significantly reduced mortality associated with human immunodeficiency virus (HIV) infection. Nonetheless, some INSTIs like dolutegravir (DTG) have been found to affect fetal development, particularly regarding neural tube defects.

In vivo studies, mainly aimed to evaluate the DTG effects on neurodevelopment, also described cardiovascular defects, prompting further investigations into DTG cardiovascular embryotoxic potential. Here we used the zebrafish embryo model to elucidate the effect of DTG exposure on cardiovascular system function and development.

Embryos were treated with DTG at several concentrations, resulting in cardiovascular toxicity, demonstrated by the presence of pericardial edema and hemorrhage. At dosage (1 μM), we found a profound impairment of cardiovascular function, characterized by decreased vessel blood flow and heartbeat.

Cardiovascular function impairments were accompanied by morphological developmental defects, characterized by shrunken atria and ventricles, altered cardiac looping and defects in angiogenesis. Molecular analysis of DTG-induced cardiovascular mechanisms of those effects revealed the DTG-induced impairment of genes that are crucial in cardiac myofibrillar organization, cardiomyocyte contractility and vascular morphogenesis and function ( myh6/amhc , myl7/cmlc2 , vegfaa , kdrl/vegfr2a , flt1/vegfr1 , hif1aa , runx1 and gata1a ).

Our exploratory findings suggest that exposure of zebrafish embryos to 1 μM DTG results in embryonic cardiovascular functional and morphological impairments, mechanistically could be linked to the disturbed regulation of key genes involved in cardiovascular development. Funding The funding for this work has been provided by the University of Brescia (60% funding to D.Z., I.Z., E.Q-R.) Author information Authors and Affiliations Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy Sara Ferretti, Daniela Zizioli, Eugenio Monti & Isabella Zanella Department of Clinical and Experimental Sciences, University of Brescia, Brescia, 25123, Italy Matteo Manenti, Giorgio Tiecco, Francesco Castelli & Eugenia Quiros-Roldan Division of Infectious and Tropical Diseases, ASST Spedali Civili di Brescia, Brescia, 25123, Italy Matteo Manenti, Giorgio Tiecco, Francesco Castelli & Eugenia Quiros-Roldan Medical Genetics Laboratory, Diagnostic Department, ASST Spedali Civili di Brescia, Brescia, Italy Isabella Zanella Authors Sara Ferretti Daniela Zizioli Matteo Manenti Giorgio Tiecco Eugenio Monti Francesco Castelli Eugenia Quiros-Roldan Isabella Zanella Corresponding author Correspondence to Eugenia Quiros-Roldan .

Ethics declarations Competing interests The authors declare no competing interests. Additional information Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material.

You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material.

If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ .

Reprints and permissions About this article Cite this article Ferretti, S., Zizioli, D., Manenti, M. et al. Insights into cardiovascular development of zebrafish embryo after exposure to dolutegravir. Sci Rep (2026). https://doi.org/10.1038/s41598-026-75116-9 Download citation Received : 03 July 2025 Accepted : 05 October 2026 Published : 11 October 2026 DOI : https://doi.org/10.1038/s41598-026-75116-9 Keywords