Exposure to Endocrine-Disrupting Chemicals and microplastics induces miswiring of GnRH3 axons in zebrafish embryos

Microplastics are becoming an increasing environmental concern. Knowledge about the possible adverse effect on human health is still poor. Early-life exposure has been linked to developmental abnormalities in humans and seems to increase the risk of endocrine and metabolic diseases later-in-life. In parallel, it has been reported that some classes of Endocrine-Disrupting Chemicals (EDCs) contained in plastics and food packaging materials may exert multiple adverse effects on hormone balance and fertility. To tackle these issues the zebrafish appears an ideal model. Previous data showed a delayed gonad maturation, decreased fertility and altered hypothalamus-pituitary-gonadal function following microplastic exposure during sensitive developmental windows. Since sexual maturation and reproduction are regulated by Gonadotropin Releasing Hormone (GnRH) expressing fibers, in this thesis I used a transgenic GnRH3:EGFP fish strain to assess whether microplastics and EDCs exposure could modify GnRH axonal pathfinding during early zebrafish neurodevelopment. Embryos were treated with increasing concentrations of a set of EDCs (Bisphenol A, Di-isodecyl-phthalate and Diethylene-glycol-dibenzoate) and microplastics (polyethylene and polystyrene). Treatments resulted in mild to severe misrouting of GnRH3 projections, showing poor fasciculation especially at the anterior commissure. Next, fish embryos were treated with combinations of microplastics and EDCs; these exhibited more severe phenotypes, but no synergism. These results suggest that these molecules are able to induce defects in the development of the neuroendocrine system. Translating to humans, the implications of these results are relevant in the contest of pre-natal exposure to EDCs and plastic microparticles, some of which have recently been found to cross the placenta.