Leydig cell regeneration from resident stem cells in a novel transgenic mouse model and impact of endocrine disruptors

Description

Leydig cells are the main source of testosterone in men. There are two distinct populations of Leydig cells: the fetal population (FLC) and the adult population (ALC). FLC are active during fetal life and produce androgens essential for fetal masculinization and male sexual differentiation. FLC disappear after birth and are replaced by ALC, which become active before puberty and remain functional throughout adult life. Testosterone produced by ALC is essential for the onset of puberty, the initiation and maintenance of spermatogenesis, and the acquisition of male physical characteristics. Leydig cells are therefore essential for male health throughout life. Abnormal Leydig cell function is associated with many pathologies ranging from under-masculinization to infertility or hypogonadism. In addition, Leydig cells are particularly sensitive to exposure to endocrine disruptors but the mechanisms remain unknown.

Using a gene editing approach, we have recently generated a new innovative transgenic mouse model that allows us to exclusively target Leydig cells. With this mouse model, it is possible to selectively destroy functional ALCs while keeping stem cells intact, and to follow the appearance of a new generation of ALCs. Using this mouse model unique to our laboratory and organ culture, the objectives of the project are to 1) study the establishment of a new generation of Leydig cells from stem cells resident in the adult testis, and 2) determine how endocrine disruptors can affect this process. This project will provide new knowledge on the ALC differentiation process and will allow us to study the mechanisms of action of endocrine disruptors. Overall, the data will contribute to our understanding of hypogonadism in humans.

In this project, the candidate will be required to work with mice (mandatory training is offered) and organ cultures. Under the supervision of a research professional, the project will involve the collection and preparation of mouse testis, thin sections, organ cultures, and direct fluorescence and immunofluorescence experiments. In addition, hormonal assays and gene expression experiments will be performed.

This project is supported by a research grant from the Natural Sciences and Engineering Research Council of Canada.

Requirements and Conditions

- Hold a BSc in biochemistry, microbiology, biology, biotechnology, or related discipline.
- Canadian citizens and permanent residents of Canada are invited to apply.
- An affinity for working with laboratory animals is essential.
- Experience with current cell and molecular biology techniques is an asset.
- Demonstrate a strong motivation for biomedical research and have good communication skills (English, French).

Send your CV, cover letter and transcripts by email to Jacques-J.Tremblay@crchudequebec.ulaval.ca. Only successful applicants will be contacted.

Application Deadline

April 1, 2025