{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T21:22:13Z","timestamp":1789680133992,"version":"4.0.1"},"reference-count":35,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,7]],"date-time":"2023-04-07T00:00:00Z","timestamp":1680825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["2765253"],"award-info":[{"award-number":["2765253"]}]},{"name":"Italian Ministry of Health","award":["2017TK7Z8L"],"award-info":[{"award-number":["2017TK7Z8L"]}]},{"name":"Italian Ministry of University and Research","award":["2765253"],"award-info":[{"award-number":["2765253"]}]},{"name":"Italian Ministry of University and Research","award":["2017TK7Z8L"],"award-info":[{"award-number":["2017TK7Z8L"]}]},{"name":"University of Milan","award":["2765253"],"award-info":[{"award-number":["2765253"]}]},{"name":"University of Milan","award":["2017TK7Z8L"],"award-info":[{"award-number":["2017TK7Z8L"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms24086913","type":"journal-article","created":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T03:26:06Z","timestamp":1681097166000},"page":"6913","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Short-Term Exposure to Benzo(a)Pyrene Causes Disruption of GnRH Network in Zebrafish Embryos"],"prefix":"10.3390","volume":"24","author":[{"given":"Ilaria","family":"Gentile","sequence":"first","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Vezzoli","sequence":"additional","affiliation":[{"name":"Division of Endocrine and Metabolic Diseases, Laboratory of Endocrine and Metabolic Research, IRCCS Istituto Auxologico Italiano, 20149 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9969-218X","authenticated-orcid":false,"given":"Sara","family":"Martone","sequence":"additional","affiliation":[{"name":"IFOM-FIRC, Institute of Molecular Oncology, 20139 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3367-7902","authenticated-orcid":false,"given":"Maria Grazia","family":"Totaro","sequence":"additional","affiliation":[{"name":"IFOM-FIRC, Institute of Molecular Oncology, 20139 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5454-6074","authenticated-orcid":false,"given":"Marco","family":"Bonomi","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, University of Milan, 20133 Milan, Italy"},{"name":"Division of Endocrine and Metabolic Diseases, Laboratory of Endocrine and Metabolic Research, IRCCS Istituto Auxologico Italiano, 20149 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2068-9581","authenticated-orcid":false,"given":"Luca","family":"Persani","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, University of Milan, 20133 Milan, Italy"},{"name":"Division of Endocrine and Metabolic Diseases, Laboratory of Endocrine and Metabolic Research, IRCCS Istituto Auxologico Italiano, 20149 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Marelli","sequence":"additional","affiliation":[{"name":"Division of Endocrine and Metabolic Diseases, Laboratory of Endocrine and Metabolic Research, IRCCS Istituto Auxologico Italiano, 20149 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,7]]},"reference":[{"key":"ref_1","first-page":"250","article-title":"The zebrafish: An emerging animal model for investigating the hypothalamic regulation of reproduction","volume":"41","author":"Bassi","year":"2016","journal-title":"Minerva Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0020-7292(00)00221-6","article-title":"Environmental influence on reproductive health","volume":"70","author":"Bhatt","year":"2000","journal-title":"Int. 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