Impact of pesticides exposition in the development on the gliovascular unit

Placental and Fetal Brain Interfaces (Royal Veterinary College, London, UK) (2025) Proc Physiol Soc 63, C02

Oral Communications: Impact of pesticides exposition in the development on the gliovascular unit

Lucie Lemale1, Rodrigo Alvear-Perez2, Véronique Perrier3, Karine Loulier3, Martine Cohen-Salmon2, Barbara Delaunay-Piednoir2

1Center for Interdisciplinary Research in Biology (CIRB), Collège de France, Université PSL, CNRS, INSERM, 75005 Paris, France. France, 2Center for Interdisciplinary Research in Biology (CIRB), CIRB, Collège de France, Université PSL, CNRS, INSERM, 75005 Paris, France. France, 3Institute for Neurosciences of Montpellier (INM), Univ Montpellier, INSERM, Montpellier, France France

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The European population is daily exposed to pesticide residues found in the food and in the drinking water. This contamination is a major public health issue as it has been link to neurodegenerative diseases (Parkinson’s and Alzheimer’s) as well as neurodevelopmental diseases (Autism spectrum disorder). To protect food consumers from potential adverse effects, European Union has set an internationally accepted maximum residue limit dose in tap water (0.1 μg/L, EU directive 2020/2184). However, it has been shown in a previous study that chronic exposure to a cocktail of fungicides at this regulatory dose altered neurogenesis in neonates following gestational exposure1. Fungicides residues may access the brain via the blood circulation and could then affect the gliovascular unit, a specific interface formed by the vascular compartment and astrocytes, where important brain functions are set such as neurovascular coupling, integrity of the blood-brain barrier, the immune homeostasis and drainage2. Thus, the chronic exposure to fungicides results in brain damage which points out the need to evaluate the impact of these residues on brain development. To do so C57Bl/6 female mice were exposed to a cocktail of fungicides (cyprodinil, mepanipyrim and pyrimethanil) at 0.1 μg/L each during gestation and breeding. To perform immunohistochemistry analysis we collected both male and female littermates brains from 5 days post-natal to adulthood. Before tissue collection, mice were injected intra-peritoneally with a mix of ketamine/xylaxine (150 and 15 mg/kg respectively).  Experiments were performed in accordance with the French ethical laws (Decree 87–848; Ministère de l’Agriculture et de la Forêt), European guidelines (Directive 2010/63/UE) and ethical committee recommendation (APAFIS #37351). All experiments were performed following the ARRIVE guidelines (www.nc3rs.org.uk), including randomization as well as blinded analysis. Data are represented as mean ± S.D. Data and statistical processing were performed using Microsoft Excel and GraphPad Prism Software. For each data set, normality was tested using Shapiro-Wilk test. Statistical significance across groups defined by one factor was performed using a Kruskall-Wallis test followed by a Dunn’s for multiple comparisons. For the pericyte and astrocyte coverage around blood vessel a Chi² test was used. A minimum of three mice per condition and four photomicrographies per mice were analyzed. The level of statistical significance was set at P < 0.05. Our preliminary results indicate that 1) microglial reactivity occurs in a sex-specific manner, 2) pericyte coverage is reduced as well as 3) perivascular astrocyte coverage but without any changes in astrocytes distribution3. This project aims to uncover early pathophysiological modifications caused by chronic exposure to fungicides, as it is essential to comprehend the impact of pesticides on brain development and warn about their usage.



Where applicable, experiments conform with Society ethical requirements.

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