Role of the transcription factor GATA4 in maintaining Leydig cell function in adults

Description

Leydig cells are the primary source of testosterone in men. There are two distinct populations of Leydig cells: the fetal population (FLC) and the adult population (ALC). FLCs are active during fetal life and produce androgens essential for fetal masculinization and male sexual differentiation. FLCs disappear after birth and are replaced by ALCs, which become active before puberty and remain functional throughout adult life. Testosterone produced by ALCs 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 numerous pathologies ranging from under-masculinization to infertility and hypogonadism.

Using a gene editing approach, we recently generated a novel transgenic mouse model that allows us to exclusively target one or the other Leydig cell population. With this mouse model, it is now possible to specifically knockout a gene in the FLC and/or ALC. The transcription factor GATA4 is essential for the development of several organs, including the gonads. In the testis, GATA4 is present in different cell types, including FLC and ALC. Our preliminary data indicate an important role for GATA4 in the establishment of ALC during development. However, a role for GATA4 in maintaining ALC function in the adult testis remains unknown. Using our laboratory proprietary mouse model, the Gata4 gene will be conditionally and inducibly knocked out exclusively in ALC of adult mice. Various experiments will then be performed on these ALCG4KO mice.

This project will establish the contribution of GATA4 in maintaining ALC function and will also allow for the study of the molecular mechanisms of GATA4 action in these cells. A loss of ALC function in the absence of functional GATA4 could explain certain cases of hypogonadism in humans.

In this project, the candidate will be required to work with mice (mandatory training is provided). Under the supervision of a research professional, the project will involve the collection and preparation of mouse testes, preparation of thin tissues sections, histology, direct fluorescence and immunofluorescence experiments. In addition, hormonal assays, gene expression (RNA-Seq and qRT-PCR), and fertility testing will be performed.

This project is supported by a research grant from the Canadian Institutes of Health Research (CIHR).

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

September 30, 2025