Estrogens originating from human and animal excretion, as well as from anthropogenic sources such as cosmetics, plastics, pesticides, detergents, and pharmaceuticals, are among the most concerning endocrine-disrupting compounds in aquatic environments due to their potent estrogenic activity. While their effects on fish reproduction are well documented, their impact on development, particularly metamorphosis, remains poorly studied. This hormonal transition, mainly controlled by the thyroid axis, is essential for the shift from the larval to the juvenile stage in teleosts.
The effects of two contraceptive estrogens on zebrafish (Danio rerio) metamorphosis were evaluated: 17α-ethinylestradiol (EE2), a synthetic reference estrogen, and estetrol (E4), a natural estrogen recently introduced in a new combined oral contraceptive formulation. Continuous exposure from fertilization to the end of metamorphosis allowed the assessment of morphological changes, disruptions of the thyroid axis, and modifications of additional molecular pathways potentially involved in metamorphic regulation.
EE2 induced significant delays and disturbances in metamorphosis, affecting both internal and external morphological traits, confirming its role as an endocrine disruptor of concern. In contrast, E4 did not cause any detectable morphological alterations even at concentrations far exceeding those expected in the environment, indicating a limited ecotoxicological risk. Molecular analyses showed that EE2 strongly affected thyroid signaling and energy metabolism during metamorphosis, whereas E4 induced only minor transcriptional and proteomic changes.
This study provides the first evidence that EE2 can disrupt zebrafish metamorphosis and highlights the importance of including this developmental stage in ecotoxicological assessments. The results also suggest a larger environmental safety margin for E4, although further research is needed to clarify the mechanisms linking estrogen exposure to metamorphic regulation.
Jury
- Prof. Frederik DE LAENDER (UNamur), Président
- Prof. Patrick KESTEMONT (UNamur), Secrétaire
- Dr Sébastien BAEKELANDT (UNamur)
- Dr Valérie CORNET (UNamur)
- Prof. Jean-Baptiste FINI (Muséum National d’Histoire Naturelle de Paris)
- Dr Marc MULLER (ULiège)
- Prof. Veerle DARRAS (KULeuven)
