Short-Term Exposure to Benzo(a)Pyrene Causes Disruption of GnRH Network in Zebrafish Embryos

Author:

Gentile Ilaria1,Vezzoli Valeria2,Martone Sara3ORCID,Totaro Maria Grazia3ORCID,Bonomi Marco12ORCID,Persani Luca12ORCID,Marelli Federica2

Affiliation:

1. Department of Medical Biotechnology and Translational Medicine, University of Milan, 20133 Milan, Italy

2. Division of Endocrine and Metabolic Diseases, Laboratory of Endocrine and Metabolic Research, IRCCS Istituto Auxologico Italiano, 20149 Milan, Italy

3. IFOM-FIRC, Institute of Molecular Oncology, 20139 Milan, Italy

Abstract

Benzo(a)pyrene (BaP), a polycyclic aromatic hydrocarbon, is considered a common endocrine disrupting chemical (EDC) with mutagenic and carcinogenic effects. In this work, we evaluated the effects of BaP on the hypothalamo-pituitary-gonadal axis (HPG) of zebrafish embryos. The embryos were treated with 5 and 50 nM BaP from 2.5 to 72 hours post-fertilization (hpf) and obtained data were compared with those from controls. We followed the entire development of gonadotropin releasing hormone (GnRH3) neurons that start to proliferate from the olfactory region at 36 hpf, migrate at 48 hpf and then reach the pre-optic area and the hypothalamus at 72 hpf. Interestingly, we observed a compromised neuronal architecture of the GnRH3 network after the administration of 5 and 50 nM BaP. Given the toxicity of this compound, we evaluated the expression of genes involved in antioxidant activity, oxidative DNA damage and apoptosis and we found an upregulation of these pathways. Consequently, we performed a TUNEL assay and we confirmed an increment of cell death in brain of embryos treated with BaP. In conclusion our data reveal that short-term exposure of zebrafish embryos to BaP affects GnRH3 development likely through a neurotoxic mechanism.

Funder

Italian Ministry of Health

Italian Ministry of University and Research

University of Milan

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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