# Nanoplastics Impair GnRH Neuron Migration and Neuroendocrine Function: Emerging Players in the Pathogenesis of Reproductive Disorders

## TL;DR

This study shows that nanoplastics can harm GnRH neurons, which control fertility, and may contribute to reproductive disorders by disrupting hormone function and cell migration.

## Contribution

The study identifies nanoplastics as potential endocrine disruptors affecting GnRH neuron function and links NPAS2 to reproductive disorders.

## Key findings

- Nanoplastics enter GnRH neurons via non-classical endocytosis and impair hormone secretion and migration.
- Transcriptomic analysis reveals gene expression changes linked to GnRH neuron development.
- Rare NPAS2 variants were found in patients with severe pubertal delay, suggesting environmental influence.

## 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.

Little is known about the effects of polystyrene nanoplastics (PS‐NPs) on gonadotropin releasing hormone (GnRH) neurons, which control puberty onset and fertility. By applying tailored in vitro GnRH neuron models, this article shows how PS‐NPs are internalized and impact hormone secretion and cell migration, through gene expression changes. Ultimately, integration of transcriptomic and human clinical data pointed out NPAS2 as a possible new environmentally influenced gene in reproductive disorders.