Innervation of the Mouse Female Reproductive System: 3D Mapping and Mechanical Insights

The NeuroSchool PhD Program of Aix-Marseille University (France) has launched its annual calls for PhD contracts for students with a master's degree in a non-French university and for  international co-supervised PhDs.

This project is one of the proposed projects. Not all proposed projects will be funded, check our website for details.

State of art: The nervous system plays a crucial in regulating the functions of the female reproductive organs. These organs demonstrate remarkable neuroplasticity, with sensory and autonomic nerve patterns changing in response to various factors, including hormonal fluctuations during the estrus cycle, pregnancy and pathological conditions such as endometriosis and cancer. This research project aims to elucidate the complex interplay between neural networks and genital organ function, focusing on the uterus and ovaries in mice.

Objectives: The project will have three objectives:

1-To create a comprehensive 3D map of uterine and ovarian innervation in adult female mice using light-sheet imaging of cleared tissues with the iDisco+ protocol combined with immunostaining. This will serve as a baseline for understanding standard innervation patterns.

2- To investigate how hormone modulations affect innervation patterns in the uterus and ovaries at different phases of the estrous cycle and during pregnancy.

3- To explore how matrix modifications of the uterus endometrium affect tissue' mechanical properties during the estrus cycle and pregnancy and to examine the relationship between tissue stiffness and innervation patterns. In this context, atomic Force Microscopy (AFM) and nanoindentation analysis on fresh flat-mount uterine preparations will be performed in control conditions and in Piezo2 mutants to explore the implication of the mechanosensitive channel in axonal remodeling associated with stiffness modifications.

Expected results: This research is expected to:

1-Provide, for the first time, a detailed 3D map of autonomic and sensory innervation in female genital organs

2-Reveal dynamic changes in innervation patterns during physiological processes and in response to hormonal fluctuations

3-Uncover the modifications of uterus stiffness during estrous cycles and its potential implication in physiological function by modulating, in particular, axonal remodeling through Piezo2 receptor.

4-Establish a foundation for future investigations into axonal remodeling in pathological conditions such as endometriosis and reproductive organ cancers.

Methods: The use of advanced 3D imaging techniques (using UltraMicroscope Blaze™ light sheet microscope, IBDM imaging platform) on cleared tissues will allow us to visualize the entire organs and give 3D innervation patterns with good preservation of spatial relationships between nerves and other structures, including uterine glands and blood vessels. Tissue stiffness will be monitored using nanoindentation (Chiaro Nanoindenter Optics11 accessible at the IBDM imaging facility) to evaluate if tissue mechanical properties are correlated to uterus modifications during estrus cycles and to establish the influence of tissue mechanics on axonal remodeling. The functional implication of Piezo2 will be evaluated using mutant mice available in the team. All antibodies to visualize autonomic and sensory innervation are accessible and have been validated for the iDisco+ clearing protocol in the team. All animals will be sacrificed according to ethical rules before organ removal (No APAFIS necessary).

Within Aix Marseille Université, NeuroMarseille brings together 8 research laboratories and NeuroSchool, a graduate school in neuroscience, to increase the attractiveness of the university, international collaborations, interdisciplinarity, links with the clinical and industrial worlds and the integration of students into professional life. 

Launched in July 2018, NeuroSchool unifies and harmonizes the training of the third year of the Bachelor of Life Sciences (Neuroscience track), the Master's and the PhD in Neuroscience. 

• Master's degree from a non-French university in neuroscience or related field
• Fluent in English

To effectively complete this project, the candidate should have a solid background in Neuroscience, Cellular and Molecular Biology, in data analysis (including image and statistical analysis methods and software) and the ability to work collaboratively as part of an international team.