Team leader : François Vialard (francois.vialard@inrae.fr)
RHuMA team includes staff from INRAE, ENVA and the University of Versailles St Quentin en Yvelines (UVSQ).
The hospitals to which the staff is attached are the CHI de Poissy-St Germain en Laye, the Foch hospital in Suresnes and Jean Verdier in Bondy.
Composition : Jean-Marc Ayoubi (PUPH), Achraf Benammar (PH), Marion Bendayan (AHU), Paul Berveiller (MCUPH), Florence Boitrelle (PUPH), Marie Carbonnel (PH), Fabienne Constant (MCF), Rodolphe Dard (PH), Maryse Dehauteur (Administrative manager), Marine Denis (AS), Dominique DeZiegler (PUPH), Marie-Noelle Dieudonné (PR), Esther Dos Santos (MCUPH), Khadija Fathallah (PH ), Laurent Galio (IR), Farah Ghieh (PhD student), Corinne Giraud (Tech), Berenice Hervé (PH), Marta Hita (PhD student), Vincent Mauffre (MCF), Denise Molina-Gomes (PH), Emmanuelle Motte-Signoret (PH), Paul Pirtea (PH),Marine Poulain (MCUPH), Mariam Raliou (IR), Yoann Rodriguez (Tech), Nelly.Swierkowski Blanchard (PH), Olivier Sandra (DR), Valerie Serazin (MCUPH), Christophe Sifer (PH). Aude Tessier (AS), François Vialard (PUPH).
Global topic
Our project aims to gain a better understanding of the cellular and molecular mechanisms of infertility by looking at all stages of reproduction, from the gamete to neonatal evaluation, in order to consider a modification of practices and/or a therapeutic approach.
In this context, animal models will allow us to circumvent certain constraints imposed by the studies in humans, while improving animal practices.
Scientific questions
Topic 1: Spermatogenesis, infertility and semen quality
- Genetics of alterations in semen quality
Among the quantitative disorders of spermatogenesis, azoospermia (absence of sperm in the ejaculate) is one of those pathologies for which the etiology is often unknown and for which the management is stereotyped and is currently limited to a testicular biopsy. Our aim is therefore to identify certain etiologies and to define the criteria to predict the presence of spermatozoa in the testicles.
Topic 2. Infertility / Inflammation and embryo-foetal-maternal interface
The quality of the embryo also depends on the quality of the gametes. However, whether in humans or in cattle, in the in vitro fertilisation (IVF) without or with intracytoplasmic sperm injection (ICSI), the choice of embryos to be transferred (on day 2, 3, 5 or 6 post-fertilisation) is essentially based on morphological and kinetic criteria. In this context, the continuous recording of embryo development represents a way to improve embryo selection criteria by allowing the observation of their morphology as well as the complete development kinetics. Our objectives are to define new decision algorithms for the embryo (human and bovine; collaboration with the EPEE team) in order to improve the pregnancy rates of the bovine and human species.
- Study of the feto-maternal interface in situations of hypofertility
The quality of the embryo influences its ability to implant in the maternal endometrium. However, alterations in the receptivity of the endometrium can also lead to a failure of embryo implantation. Maternal obesity, characterised by hyperinflammation, is associated with hypofertility. Our objectives are to (i) study the impact of maternal obesity on human placental functions and uterine receptivity, and (ii) identify biomarkers (local and peripheral) of uterine receptivity and inflammation (e.g. subclinical endometritis) in livestock animal models and in women undergoing IVF treatment. This could allow us to show that endometritis, as in the cow, is a factor in reproductive failure and therefore to propose an adapted treatment.
Topic 3. Therapeutic approaches and development of study models
In the context of the creation of the first French university chair of transplantation (UVSQ), our objective is to master the transplantation of uterus in the ewe. This approach is an alternative to surrogate motherhood, which raises numerous ethical questions. The objectives of this approach are: (1) to allow pregnancy in women without a uterus (hysterectomy, Rokitansky-Küster-Hauser syndrome), (2) to evaluate the impact of this graft on the quality of the endometrium, (3) to define a new model of gestation disruption in animals.
- Ex-utero pregnancy in the preterm lamb
This project aims to realise an extra-uterine fetal development system (Partridge et al, 2017), in order to create a unique pathophysiological model to analyse in detail the fetal development depending on the environment and its variations (metabolic, hormonal, hemodynamic, inflammatory...). The objectives of this project are (i) to characterise the impact of prematurity on organ development (brain, lungs) and (ii) to develop a model of extra-uterine gestation in order to be able, in the long term, to use it to study the impact of the transplacental passage of exogenous molecules (drugs, pollutants…) on foetal development. Finally, this project could be of major help in the management of extreme prematurity (birth before 28 weeks of amenorrhea), a real public health problem, particularly in the Western world, where it is the leading cause of neonatal morbidity and mortality.
- Transplacental passage study
The concomitant occurrence of cancer and pregnancy affects approximately 1 in 1,000 pregnancies. The management of a pregnant woman with cancer requires a multidisciplinary approach that must take into account the benefit-risk ratio for the mother and the foetus. This choice is possible through the evaluation of several parameters, including the possibility of transplacental transfer and the risk of teratogenicity of drugs. Our team has developed a placental perfusion model in order to be able to evaluate the transplacental passage of therapeutic molecules and their derivatives with the aim of responding as quickly as possible to questions when new molecules appear.
- Towards a new treatment for Down Syndrome
Trisomy 21 is the most common genetic syndrome in the general population with 1 in 700 births. However, no therapy has been developed to reduce the impact of the presence of 3 chromosomes 21 on brain development and the occurrence of delayed acquisition. The objective of this work is to test, in the prenatal and perinatal period, the effect of an anti-inflammatory treatment in a mouse model for trisomy 21. The treatment will also be carried out on wild mice in order to evaluate possible side effects.
- Development of complex in vitro systems, such as organoids
The use of animal models is still nowadays a mainstay of therapeutic evaluation. Our goal is to develop new approaches using complex cellular models such as (i) uterine organoids to study the impact of endometrial pathologies such as endometritis or endometriosis on uterine receptivity, and (2) brain organoids to evaluate new treatments for Down syndrome.
Expertise
Animal species (cattle, sheep) and human
Disciplinary and technical skills:
- Physiology : placental perfusion
- Animal experimentation
- Histology-Immunohistology
- Gene expression: RT-qPCR, transcriptome analysis in collaboration with the UFR SVS genomics platform (UVSQ)
- Cell biology : primary cultures of trophoblastic and endometrial cells, uterine organoids
- Biochemistry : clinical and fundamental biochemistry
- Genomics
Research facilities
The experimental programmes are conducted in close interaction with the INRAE SAAJ experimental unit and the ENVA. Most of our programmes rely on the resources and skills of the Jouy en Josas centre and the UFR S. Veil-Santé (UVSQ):
- In vivo and in vitro imaging platform MIMA2 (INRAE) and imaging and cytometry platform CYMAGE (UVSQ-UFR S Veil-Santé)
- Transcriptomics and histology platform @Bridge (INRAE)
- Genomics platform (UVSQ-UFR S Veil-Santé)
- Surgical and imaging platform CIMA (INRAE)
- Placental perfusion platform (UVSQ-UFR S Veil-Santé)
- Histology platform (UVSQ-UFR S Veil-Santé)
