Multi Species Analyses Reveal Testicular T3 Metabolism and Signalling as a Target of Environmental Pesticides

Author:

Nittoli Valeria,Colella Marco,Porciello Alfonsina,Reale CarlaORCID,Roberto Luca,Russo Filomena,Russo Nicola A.,Porreca Immacalata,De Felice MarioORCID,Mallardo Massimo,Ambrosino ConcettaORCID

Abstract

Thyroid hormones (THs) regulate many biological processes in vertebrates, including reproduction. Testicular somatic and germ cells are equipped with the arrays of enzymes (deiodinases), transporters, and receptors necessary to locally maintain the optimal level of THs and their signalling, needed for their functions and spermatogenesis. Pesticides, as chlorpyrifos (CPF) and ethylene thiourea (ETU), impair the function of thyroid and testis, affecting male fertility. However, their ability to disarrange testicular T3 (t-T3) metabolism and signalling is poorly considered. Here, a multi-species analysis involving zebrafish and mouse suggests the damage of t-T3 metabolism and signalling as a mechanism of gonadic toxicity of low-doses CPF and ETU. Indeed, the developmental exposure to both compounds reduces Dio2 transcript in both models, as well as in ex-vivo cultures of murine seminiferous tubules, and it is linked to alteration of steroidogenesis and germ cell differentiation. A major impact on spermatogonia was confirmed molecularly by the expression of their markers and morphologically evidenced in zebrafish. The results reveal that in the adopted models, exposure to both pesticides alters the t-T3 metabolism and signalling, affecting the reproductive capability. Our data, together with previous reports suggest zebrafish as an evaluable model in assessing the action of compounds impairing locally T3 signalling.

Funder

Regione Campania

Istituto Nazionale per l'Assicurazione Contro Gli Infortuni sul Lavoro

Publisher

MDPI AG

Subject

General Medicine

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