Endocrine and systemic toxicity of pyriproxyfen in adult female zebrafish: disruption of the HPT axis and peripheral organ impairments
5 affiliations
- 1Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
- 2Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
- 3Cancer Signaling and Metabolism Group, i3S – Institute for Research and Innovation in Health, University of Porto, Porto, Portugal
- 4Department of Pathology, Faculty of Medicine, University of Porto, Porto, Portugal
- 5Laboratory of Experimental Endocrinology-LEEx, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
Abstract
Endocrine-disrupting chemicals (EDCs) can destabilize the hypothalamic–pituitary–thyroid (HPT) axis, a fundamental regulator of vertebrate development and metabolism. Pyriproxyfen (PPF), a juvenile hormone analog widely utilized in vector control, is recommended by the World Health Organization (WHO) for application at concentrations of up to 10 µg/L in drinking water; however, its safety profile for vertebrates remains a matter of concern. In this study, we investigated the endocrine and systemic impacts of PPF in adult female zebrafish exposed for 14 days to 1, 10, or 100 µg/L. Histological, hormonal, and transcriptional analyses across the thyroid, brain, liver, and kidney revealed a non-monotonic response centered on the WHO reference application concentration. The 10 µg/L group exhibited the most significant molecular impairment in the thyroid, characterized by the upregulation of slc5a5 (nis), nkx2.1, pax2a, and tshr, while repressing thyroglobulin (tg) expression. Consistent with these molecular alterations, thyroid epithelial disruption was observed at 1 and 10 µg/L. In contrast, exposure to 100 µg/L increased plasma TSH levels and the expression of pituitary tshb and hepatic dio1, suggesting a compensatory response of the HPT axis. Renal morphometry additionally revealed tubular alterations across all exposure groups. Overall, these findings demonstrate a non-monotonic concentration–response centered on 10 µg/L as a key mechanistic feature of PPF toxicity and support further evaluation of thyroid and renal endpoints in ecotoxicological risk assessment.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s11356-026-38319-1.
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BibTeX
@article{cabral2026endocrine,
title = {{Endocrine and systemic toxicity of pyriproxyfen in adult female zebrafish: disruption of the HPT axis and peripheral organ impairments}},
author = {Andressa Pereira Cabral and Fabricio Pereira dos Santos Maia and Damáris Barcelos Cunha Azeredo and Andréa Souza de Jesus Santana and Lycia de Brito Gitirana and John Lennon de Paiva Coimbra and Denise Pires de Carvalho and Paula Soares and Eduardo Rios-Morris and Leandro Miranda-Alves},
journal = {Environmental Science and Pollution Research International},
year = {2026},
month = oct,
doi = {10.1007/s11356-026-38319-1},
url = {https://doi.org/10.1007/s11356-026-38319-1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Endocrine and systemic toxicity of pyriproxyfen in adult female zebrafish: disruption of the HPT axis and peripheral organ impairments
AU - Andressa Pereira Cabral
AU - Fabricio Pereira dos Santos Maia
AU - Damáris Barcelos Cunha Azeredo
AU - Andréa Souza de Jesus Santana
AU - Lycia de Brito Gitirana
AU - John Lennon de Paiva Coimbra
AU - Denise Pires de Carvalho
AU - Paula Soares
AU - Eduardo Rios-Morris
AU - Leandro Miranda-Alves
PY - 2026
DA - 2026/10/19
JO - Environmental Science and Pollution Research International
DO - 10.1007/s11356-026-38319-1
UR - https://doi.org/10.1007/s11356-026-38319-1
AB - Endocrine-disrupting chemicals (EDCs) can destabilize the hypothalamic–pituitary–thyroid (HPT) axis, a fundamental regulator of vertebrate development and metabolism. Pyriproxyfen (PPF), a juvenile hormone analog widely utilized in vector control, is recommended by the World Health Organization (WHO) for application at concentrations of up to 10 µg/L in drinking water; however, its safety profile for vertebrates remains a matter of concern. In this study, we investigated the endocrine and systemic impacts of PPF in adult female zebrafish exposed for 14 days to 1, 10, or 100 µg/L. Histological, hormonal, and transcriptional analyses across the thyroid, brain, liver, and kidney revealed a non-monotonic response centered on the WHO reference application concentration. The 10 µg/L group exhibited the most significant molecular impairment in the thyroid, characterized by the upregulation of slc5a5 (nis), nkx2.1, pax2a, and tshr, while repressing thyroglobulin (tg) expression. Consistent with these molecular alterations, thyroid epithelial disruption was observed at 1 and 10 µg/L. In contrast, exposure to 100 µg/L increased plasma TSH levels and the expression of pituitary tshb and hepatic dio1, suggesting a compensatory response of the HPT axis. Renal morphometry additionally revealed tubular alterations across all exposure groups. Overall, these findings demonstrate a non-monotonic concentration–response centered on 10 µg/L as a key mechanistic feature of PPF toxicity and support further evaluation of thyroid and renal endpoints in ecotoxicological risk assessment. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s11356-026-38319-1.
SN - 0944-1344
SN - 1614-7499
ER -