Differential effects of 3,5-T2 and T3 on the gill regeneration and metamorphosis of the Ambystoma mexicanum (axolotl)


Por: Lazcano, I., Olvera, A., Pech-Pool, S. M., Sachs, L., Buisine, N., Orozco, A.

Publicada: 10 jul 2023
Categoría: Endocrinology, diabetes and metabolism

Resumen:
Thyroid hormones (THs) regulate tissue remodeling processes during early- and post-embryonic stages in vertebrates. The Mexican axolotl (Ambystoma mexicanum) is a neotenic species that has lost the ability to undergo metamorphosis; however, it can be artificially induced by exogenous administration of thyroxine (T4) and 3,3 & PRIME;,5-triiodo-L-thyronine (T3). Another TH derivative with demonstrative biological effects in fish and mammals is 3,5-diiodo-L-thyronine (3,5-T2). Because the effects of this bioactive TH remains unexplored in other vertebrates, we hypothesized that it could be biologically active in amphibians and, therefore, could induce metamorphosis in axolotl. We performed a 3,5-T2 treatment by immersion and observed that the secondary gills were retracted, similar to the onset stage phenotype; however, tissue regeneration was observed after treatment withdrawal. In contrast, T4 and T3 immersion equimolar treatments as well as a four-fold increase in 3,5-T2 concentration triggered complete metamorphosis. To identify the possible molecular mechanisms that could explain the contrasting reversible or irreversible effects of 3,5-T2 and T3 upon gill retraction, we performed a transcriptomic analysis of differential expression genes in the gills of control, 3,5-T2-treated, and T3-treated axolotls. We found that both THs modify gene expression patterns. T3 regulates 10 times more genes than 3,5-T2, suggesting that the latter has a lower affinity for TH receptors (TRs) or that these hormones could act through different TR isoforms. However, both TH treatments regulated different gene sets known to participate in tissue development and cell cycle processes. In conclusion, 3,5-T2 is a bioactive iodothyronine that promoted partial gill retraction but induced full metamorphosis in higher concentrations. Differential effects on gill retraction after 3,5,-T2 or T3 treatment could be explained by the activation of different clusters of genes related with apoptosis, regeneration, and proliferation; in addition, these effects could be initially mediated by TRs that are expressed in gills. This study showed, for the first time, the 3,5,-T2 bioactivity in a neotenic amphibian.

Filiaciones:
Lazcano, I.:
 Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Querétaro, Mexico

Olvera, A.:
 Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Querétaro, Mexico

Pech-Pool, S. M.:
 Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Querétaro, Mexico

Sachs, L.:
 UMR PhyMA CNRS, Muséum National d’Histoire Naturelle, Paris, France

Buisine, N.:
 UMR PhyMA CNRS, Muséum National d’Histoire Naturelle, Paris, France

Orozco, A.:
 Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Querétaro, Mexico

 Escuela Nacional de Estudios Superiores, Unidad Juriquilla, Universidad Nacional Autónoma de México (UNAM), Querétaro, Mexico
ISSN: 16642392





Frontiers in Endocrinology
Editorial
Frontiers Research Foundation, PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND, Suiza
Tipo de documento: Article
Volumen: 14 Número:
Páginas:
WOS Id: 001031935000001
ID de PubMed: 37492199
imagen Green Published, gold, All Open Access; Gold

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