Researchers Involved
Researchers who have worked on this axis:
- Prof. F. Paris
- Prof. E. Huyghe
- Dr. G. Perez
- Dr. R. Mieusset
- Dr. S. Hamdi
To contact a reference person for this research axis, please call Françoise Paris at 06 15 10 63 71.
1 – Phenotypic and molecular analysis of infertile populations and/or those with genital developmental anomalies
Researchers who have worked on this axis:
- Prof. F. Paris
- Prof. E. Huyghe
- Dr. R. Mieusset
- Dr. S. Hamdi
a) Problem Statement
Regional involvement in the theme
To address this issue, uniting our forces has been a real asset in improving patient phenotyping and molecular research
- Anomalies of the male genital tract (Dr. Mieusset, Dr. Hamdi, Prof. Huyghe)
- Clinical phenotyping (seminal vesicles, epididymis, deferens, kidneys), biological (gonadotropic axis, seminal markers), genetic CFTR (Palat et al., 2016) and ADGRG2 (Mieusset et al. 2017)
- VDG (DSD) / Cryptorchidism – Complex DSD 1/5000, cryptorchidism 1% (Prof. Kalfa and Prof. Paris) and Whole genome sequencing (Prof. Paris)
- Clinic Toulouse + Montpellier
- VDG Molecular Biology Diagnostic Department (Prof. Paris, Paris et al 2013, Paris et al 2018)
- Involvement / impact of EDCs (Kalfa, Paris et al 2019, Paris et al 2006)
The importance of precise phenotyping
Developmental anomalies of the male genital tract span a spectrum ranging from variations in genital development (VDG), or Disorders of Sex Development (DSD), through isolated anomalies of the efferent ducts, cryptorchidism, to infertility. It is essential to accurately phenotype these patients clinically, hormonally, ultrasonographically, and molecularly to better understand the underlying mechanisms of these anomalies and their impact, particularly on fertility.
Outline of VDG
b) Projects
- Evaluate our cohorts of VDG patients followed in Toulouse and Montpellier regarding their sexuality and fertility (Prof. Huyghe, Prof. Paris, Dr. Almont and Dr. Baudin)
- Develop molecular biology tools (minigene bank) to better understand the mechanistic basis of molecular anomalies found, within the genetics laboratory (Prof. Paris) of CRDevGen, in VDG patients, with a particular focus on intronic variants (Prof. Paris, Ms. Gennetier)
2 – Organoids of seminiferous tubules, epididymis, and deferens
Researchers who have worked on this axis:
- Prof. E. Huyghe
- Dr. G. Perez
a) Problem Statement
- A major problem in reproductive biology and medicine is the absence of target organ models
- Conventional cell cultures do not reflect the spatial complexity of tissues
- Animal models yield irreproducible results: reproduction is the most divergent function between species.
b) ORHUMAN Project
ORHUMAN: HUman Male REproductive ORganoids
The solution: organoids of seminiferous tubules, epididymis, and deferens.
- Organoids are three-dimensional structures derived from adult or pluripotent stem cells.
- Fundamental characteristic: the capacity for self-organization of cultured cells, reminiscent of a developmental program.
- Obtaining a miniaturized pseudo-organ (200μm to 1000μm) hosting all cell types of the organ in question and exhibiting a function similar to the original tissue
The solution: human organoids of seminiferous tubules, epididymis, and deferens.
- Seminiferous tubule organoids: pluripotent cells; the culture method to differentiate iPSCs (or ECs) into Sertoli cells is known (addition of BMP4, FGF9, Activin A to culture media)
- Epididymis and deferens organoids: adult stem cells currently being characterized (double labeling* – intracellular and surface)
- A major innovation used: a novel culture process (non-public due to patent)
Cells will be obtained from brain-dead patients (PMO) -> the protocol is approved and registered with the ABM under No. PFS19-010.
Human male tract organoids (Dr. G. Perez, R. Soudy. DEFE)
- Funding: Occitanie Region and Urosphère SAS company (36-month renewable funding)
- Partnership: Urosphere SAS and Inserm U1220 (hosts the “Organoids” platform labeled GIS IBiSA). A collaboration in 2016 between Urosphere and U1220 led to the development of the first human bladder organoid cultures.
- ORHUMAN Duration: Minimum 5 years, starting February 2020.
- Personnel:
- One postdoctoral researcher is recruited full-time for the project
- One research engineer from Urosphere is assigned to the project
- One to two doctoral students will be trained through the project
- Interns will be hosted throughout the project period
- A training module in doctoral school (ED BSB) may be offered.
