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Molecular Mechanisms and Pathways Involved in Toxicant-Induced Stress

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: 31 July 2026 | Viewed by 675

Special Issue Editors


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Guest Editor
1. Department of Environmental and Biological Sciences and Technologies (DiSTeBA), University of Salento, Via per Monteroni, 73100 Lecce, Italy
2. National Biodiversity Future Center (NBFC), 90133 Palermo, Italy
Interests: oxidative stress; carbonic anhydrase; pollution biomarkers; ion transport; epithelia; physiological responses to pollutants; impact of nanoplastics on human and wildlife health; health-related toxicity of airborne particles
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Environmental and Biological Sciences and Technologies (DiSTeBA), University of Salento, Via per Monteroni, 73100 Lecce, Italy
Interests: ion homeostasis; osmoregulation; oxidative stress; toxicology; cell volume regulation; toxicological effects of particulate matter; nanoplastics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Environmental and occupational exposure to chemical toxicants induces a wide spectrum of molecular and cellular responses that are intricately linked to oxidative stress and the activation of signaling pathways, leading to downstream toxic effects. In recent years, mechanistic insights into toxicant actions have led to the identification and characterization of molecular biomarkers, which have emerged as powerful tools for the early detection of toxicant exposure and risk assessment.

This Special Issue aims to gather cutting-edge research and comprehensive reviews that shed light on the molecular mechanisms and pathways involved in toxicant-induced stress. We invite contributions that explore toxicant-related oxidative stress pathways, redox-sensitive signaling networks, cell injury pathways, and the development of molecular biomarkers across various model systems.

By advancing our understanding of the molecular mechanisms and pathways involved in toxicant-induced stress, this Special Issue contributes to the development of more precise diagnostic and preventive approaches in environmental health and toxicology.

Dr. Maria Giulia Lionetto
Dr. Maria Giordano
Guest Editors

Manuscript Submission Information

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Keywords

  • oxidative stress
  • cell death
  • biomarkers
  • toxicant exposure
  • environmental toxicology
  • cell signaling pathways

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Published Papers (1 paper)

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Research

22 pages, 7222 KB  
Article
Cadmium Impairs Human GnRH Neuron Development: Mechanistic Insights into Reproductive Dysfunction
by Giulia Guarnieri, Jacopo J. V. Branca, Rachele Garella, Letizia Lazzerini, Flavia Mencarelli, Francesco Palmieri, Paolo Comeglio, Matteo Becatti, Mario Maggi, Massimo Gulisano, Alessandra Pacini, Roberta Squecco and Annamaria Morelli
Int. J. Mol. Sci. 2026, 27(3), 1221; https://doi.org/10.3390/ijms27031221 - 26 Jan 2026
Cited by 1 | Viewed by 443
Abstract
There is increasing evidence that exposure to environmental toxicants may impact fertility, especially during critical windows of reproductive axis development. Hypothalamic gonadotropin-releasing hormone (GnRH) neurons, essential for puberty onset and fertility, originate from the olfactory placode and migrate toward the hypothalamus during development, [...] Read more.
There is increasing evidence that exposure to environmental toxicants may impact fertility, especially during critical windows of reproductive axis development. Hypothalamic gonadotropin-releasing hormone (GnRH) neurons, essential for puberty onset and fertility, originate from the olfactory placode and migrate toward the hypothalamus during development, making them particularly vulnerable to environmental insults. Cadmium (Cd), a widespread heavy metal, is well known for its gonadotoxicity, but its impact on human hypothalamic neuron development remains unclear. Using human fetal GnRH neuroblasts (FNCB4) we investigated the effects of Cd exposure on their morpho-functional and developmental features. Cd induced oxidative stress and COX2 mRNA upregulation, indicative of inflammatory pathway activation, which was accompanied by reduced cell migration and downregulation of motility-related genes. These effects were associated with F-actin disassembly and altered expression of adhesion molecules. Electrophysiological analyses showed that Cd altered membrane potential, increased capacitance and permeability, and disrupted gap junctional communication, as also confirmed by connexin-43 delocalization. Moreover, Cd significantly reduced the expression of specific GnRH neuronal markers, suggesting impaired functional maturation. Overall, our findings provide the first evidence that Cd may interfere with mechanisms crucially involved in human GnRH neuron development, adding new mechanistic insights into the comprehension of how early-life exposure to Cd may contribute to fertility concerns. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Pathways Involved in Toxicant-Induced Stress)
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