Effects of benzo[a]pyrene on the reproductive axis: Impairment of kisspeptin signaling in human gonadotropin-releasing hormone primary neurons.

Autor: Guarnieri G; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy., Becatti M; Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', University of Florence, Florence, Italy., Squecco R; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy., Comeglio P; Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', University of Florence, Florence, Italy., Garella R; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy., Tamburrino L; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy., Marchiani S; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy., Vignozzi L; Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', University of Florence, Florence, Italy; I.N.B.B. (Istituto Nazionale Biostrutture e Biosistemi), Rome, Italy., Vannelli GB; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy., Maggi M; Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', University of Florence, Florence, Italy; I.N.B.B. (Istituto Nazionale Biostrutture e Biosistemi), Rome, Italy., Morelli A; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy. Electronic address: a.morelli@unifi.it.
Jazyk: angličtina
Zdroj: Environmental pollution (Barking, Essex : 1987) [Environ Pollut] 2023 Jan 15; Vol. 317, pp. 120766. Date of Electronic Publication: 2022 Nov 29.
DOI: 10.1016/j.envpol.2022.120766
Abstrakt: The neuroendocrine control of reproduction is strictly coordinated at the central level by the pulsatile release of gonadotropin-releasing hormone (GnRH) by the hypothalamic GnRH neurons. Alterations of the GnRH-network, especially during development, lead to long-term reproductive and systemic consequences, also causing infertility. Recent evidence shows that benzo[a]pyrene (BaP), a diffuse pollutant that can play a role as an endocrine disruptor, affects gonadal function and gamete maturation, whereas data demonstrating its impact at hypothalamic level are very scarce. This study investigated the effects of BaP (10 μM) in a primary cell culture isolated from the human fetal hypothalamus (hfHypo) and exhibiting a clear GnRH neuron phenotype. BaP significantly decreased gene and protein expression of both GnRH and kisspeptin receptor (KISS1R), the master regulator of GnRH neuron function. Moreover, BaP exposure increased phospho-ERK1/2 signaling, a well-known mechanism associated with KISS1R activation. Interestingly, BaP altered the electrophysiological membrane properties leading to a significant depolarizing effect and it also significantly increased GnRH release, with both effects being not affected by kisspeptin addition. In conclusion, our findings demonstrate that BaP may alter GnRH neuron phenotype and function, mainly interfering with KISS1R signaling and GnRH secretion and therefore with crucial mechanisms implicated in the central neuroendocrine control of reproduction.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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