Nanoplastics Impair GnRH Neuron Migration and Neuroendocrine Function: Emerging Players in the Pathogenesis of Reproductive Disorders
Source abstract
Abstract
ABSTRACT Nanoplastics (NPs) pose an emerging threat to environmental and human health. Still, the impacts of NPs on the endocrine control of reproduction remain poorly understood, despite increasing trends of infertility worldwide. In mammals, reproductive function relies on the hypothalamus‐pituitary‐gonadal axis, centrally regulated by gonadotropin‐releasing hormone (GnRH) neurons. Disruption in GnRH neuron development or function leads to GnRH deficiency (GD), a genetic condition presenting delayed puberty and infertility. Yet, genetic causes explain only ∼50% of GD cases, suggesting a role for environmental factors in disease etiology. Here, we investigate NP effects on GnRH neuron biology by applying two established in vitro models: hormone‐secreting GT1‐7 cells and migrating GN11 cells. We show that NPs enter cells via non‐classical endocytosis, alter neuroendocrine function in GT1‐7 cells, and impair migration in GN11 cells. Transcriptomic analysis of NP‐exposed GN11 cells reveals differential expression of key genes linked to GnRH neuron development. Moreover, integrating these findings with exome sequencing data from patients with GD identifies rare NPAS2 variants in two males with severe pubertal delay. These results suggest that PS‐NPs disrupt key physiological functions of GnRH neurons and may act as novel endocrine disruptors, contributing to the pathogenesis of reproductive disorders.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Microplastics and Plastic Pollution · Effects and risks of endocrine disrupting chemicals · biodegradable polymer synthesis and properties
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti” Università degli Studi di Milano Milan Italy
Department of Life Sciences and Systems Biology Università di Torino Turin Italy
Department of Molecular Biotechnology and Science for Health Università di Torino Turin Italy
Lister Hospital East and North Hertfordshire Teaching NHS Trust Stevenage UK
Department of Paediatric Endocrinology Barts Health NHS Trust London UK
Genetic Endocrinology Unit (LIM25) Endocrinology Division Faculdade De Medicina da Universidade de São Paulo (HC‐FMUSP) São Paulo Brazil
SUSPLAS@UniTo Sustainable Plastic Scientific Hub Università di Torino Turin Italy
Centre for Endocrinology William Harvey Research Institute Barts, and the London School of Medicine and Dentistry Queen Mary University of London London UK
Coordinating Research Center on Nano/microplastics on Environments Medicine Ecology Systems Interaction Studies – CRC NEMESIS Università degli Studi di Milano Milan Italy
Funding
Wellcome Trust · Barts Charity · Conselho Nacional de Desenvolvimento Científico e Tecnológico · Ministero dell'Università e della Ricerca · Society of Toxicology · Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
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