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

Cells

Marco Colella¹  Valeria Nittoli¹  Alfonsina Porciello¹  Concetta Ambrosino¹  Luca Roberto¹  Immacalata Porreca¹  Filomena Russo¹  Carla Reale¹  Nicola A. Russo¹  Mario De Felice²  Massimo Mallardo² 

[1] Biogem, Istituto di Biologia e Genetica Molecolare, Via Camporeale, 83031 Ariano Irpino (AV), Italy;Department of Molecular Medicine and Medical Biotechnologies, University of Naples “Federico II”, 59100 Naples, Italy;

关键词: pesticides;    T3 signalling and metabolism;    cross-species analysis;    testis;    fertility;   

DOI  :  10.3390/cells10092187

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown