Team
Genetics, Epigenetics and therapies of infertility
Dpt: Environnement, Reproduction, Infections, Cancer
Our research activities
Infertility is a common condition and 1 in 7 couples will need medical assistance to procreate. For couples with the most severe phenotypes, their management will require the use of medically assisted reproduction techniques, which are complex and have a significant financial cost. Among these couples, 1 out of 2 will come out of this difficult process without a child, with important consequences in terms of well-being for the couples involved. Two major reasons explain these failures: 1/ our poor understanding of the molecular pathogenesis of many infertilities and 2/ these techniques are only palliative and do not restore the deficient functions of the gametes or the reproductive system of the patients. To address these major problems of infertility, we have developed a research program aimed at:
- characterize the genes involved in male and female infertility
- to understand the cellular role of the identified proteins and thus to discover new actors of gametogenesis. This also allows us to characterize the molecular pathogenesis of infertility.
- to propose improvements or alternative therapies in the field of male infertility, taking into account our findings on the causes of infertility.
Christophe ARNOULT
Team leader
Pierre RAY
Team leader
Our research axes
This work is based on an exceptional private cohort of patients whose exomic sequencing has been progressively performed over the last 5 years (~450 exomes now available) In recent years, we have focused on 4 infertility phenotypes: 1) macrozoospermia, 2) globozoospermia, 3) multiple morphological abnormalities of the flagellum (MMAF) and 4) non-obstructive azoospermia (NOA). Our strategy is the following: a) recruitment of consanguineous patients, b) genetic analysis by exome sequencing, c) identification of pathogenic mutations …
The role of most of the identified proteins is little or not known. The objective of this part of the research program is to characterize the localization, the molecular partners and the function of the protein. This work relies on the creation of specific tools (antibodies, KO mice, transgenic mice with (fluorescent) labelled protein) and to better understand gametogenesis by characterizing new molecular actors and new signaling pathways but also to improve our knowledge of the molecular pathogenesis.
In spite of the remarkable progress made in recent decades in the treatment of infertility, 1 couple out of 2 remains in therapeutic failure. Our goal is to develop new therapeutic strategies for these couples or to improve current techniques. The identification of the genetic causes of male infertility allows us to evaluate a new approach in the treatment of infertility, based on the restoration of the deficient protein in gametogenesis. We are also developing studies of new therapeutic strategies in the bovine species, where medically assisted …
Our major publications
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Our collaborations
- Sege Nef Unige, Genève, Switzerland - Generation of models to study gametogenesis
- Rafael Fissore Umass, Mass, USA - Study of oocyte activation
- Rahouda Zouari Clinique des Jasmins, Tunisia - Patient’s recruitment
- Amir Aminiri Royan institute, Iran - Patient’s recruitment and molecular biology
- Feng Zhang Fudan University, Shanghai, China - Genetics of MMAF patients Generation of animal models
- Nicolas Tierry-Mieg CNRS, TIMC, University of Grenoble - Analyses of genome wide data
- Gérard Lambeau CNRS, IPMC, University of Sophia - Antipolis Role of sPLA2 in embryonic development
- Mélanie Bonhivers CNRS, Bordeaux - Trypanosoma models for MMAF
- Michael Mitchell Aix-Marseille University - Genetics of azoospermia
- Cedric Allier Univ. Grenoble Alpes, CEA, LETI, DTBS, 38000, Grenoble, France - Development of holographic microscopy
- Aminata Touré IAB - Characterization of genes involved in flagellum defects
- Saadi Khochbin IAB - Epigenetic of sperm
- Stefan Dimitrov IAB - Importance of H3.3 in spermatogenesis
Our technologies
- Technique de procréation médicalement assistée (CASA, IVF, ICSI et IUU)
- Biologie moléculaire et séquençage
- Biochimie
- Microscopie