3 years PhD position on the mechanisms of adult chronic exposure to phthalates in the male brain

The research project will be carried out under the supervision of S. Mhaouty-Kodja at the « Neuroplasticity of Reproductive Behaviors » team (Sorbonne Université – Institut de Biologie Paris-Seine, Neurosciences Paris-Seine, CNRS UMR 8246 / INSERM U1130, Paris).

Application deadline: 15th October 2018

Starting date: 1st January 2019

Project description: Phthalates are organic pollutants widely detected in the environment. This results in a large contamination of wild life and adult individuals in industrialized countries. In this context, the team recently showed that exposure of adult male mice to environmental doses of phthalates, in particular di-(2-e?thylexyl)phthalate (DEHP), lowers the emission of ultrasonic vocalizations and attractiveness, and delays the initiation of mating (Dombret et al. 2017). This sexual vulnerability is not due to changes in circulating levels of testosterone or integrity of the gonadotropic axis, but rather to down- regulation of the androgen receptor in the neural circuitry involved in the expression of sexual behavior. This receptor plays a key and complementary role to that of estrogen receptors alpha in the activation of this behavior by gonadal testosterone (Raskin et al. 2009; Picot et al. 2014). The proteomic analysis of the preoptic nucleus, an hypothalamic region implicated in the expression of sexual behavior, highlighted a protein network involving the AR and a majority of proteins differentially expressed between the control and DEHP-exposed groups. These proteins play roles in cellular functions such as metabolism, neuroinflammation... This project aims to i) characterize the behavioral effects of exposure to low doses of DEHP alone or in an environmental mixture in male mice, ii) determine the cellular pathways associated with these behavioral alterations and ii) understand the link between reduced neural sensitivity to androgens and induced alterations in genetic models invalidated for relevant sex steroid receptors in the nervous system.

Techniques used in the project: behavioral tests, immunohistochemistry, Western blotting, qRT-PCR...

Application:

The candidate should hold a Master 2 in neuroscience or neuroendocrinology. The application must include:

1- Letter of motivation
2- Curriculum Vitae
3- Master transcript and copies of diplomas or attestations
4- Names and contact of two referees

Please send the application letter to sakina.mhaouty-kodja@upmc.fr