Effects of 500nm polystyrene nanoplastic exposure on immortlized GnRH neurons

Plastic pollution, especially from mismanaged waste degrading into nanoplastics (NPs), poses a growing threat to environmental and human health. Polystyrene NPs (PS-NPs) are particularly prevalent, infiltrating ecosystems and accumulating in organs, including the brain. While NPs are linked to behavioral, metabolic, and developmental effects, their impact on reproduction and fertility remains poorly understood. Declining fertility rates suggest environmental toxicants like NPs may contribute to adverse reproductive outcomes. Reproductive function relies on the hypothalamus-pituitary-gonad (HPG) axis, centrally regulated by gonadotropin-releasing hormone (GnRH) neurons. These neurons originate in the nasal placode and migrate to the hypothalamus during embryogenesis. Altered GnRH neuron development or release can lead to absent puberty and infertility, whose genetic causes explain only 50% of known cases. In this context, environmental factors including NPs might contribute to the etiology of these disorders. In this work, we take advantage of an established model of migrating GnRH neurons (GN11) to assess PS-NPs effects and to provide the first evidence that these environmental factors interfere with cellular and molecular processes of GnRH neurons, thus suggesting a novel mechanism contributing to idiopathic infertility.