Team 2b : Understanding embryo development to improve fertility

Team 2a leaders: Dr. Jérôme Jullien and Dr. Laurent David

Research program

Our team uses a combination of models to understand early embryonic development, with the goal of improving IVF.

1) Epigenetic programming of sperm for the regulation of early embryonic development.

At fertilization the sperm delivers to the embryo paternal genomic information, as well as epigenetic information such as those encoded in DNA methylation, post translational modifications of histones, and small RNAs. We are interested in evaluating the contribution of these epigenetic cues in the normal development of embryos, in particular in the regulation of gene expression and the establishment of early embryonic cell fate. We also investigate how such sperm-mediated epigenetic inheritance could be hijacked to transmit paternal experience of the environment to the next generation.

2) Epigenetic reprogramming of cell fate.

During development, cells acquire distinct cell fate that need to be stabilized in order to ensure organismal health. We aim to identify the epigenetic mechanisms involved in the stabilization of cell identity. To that end, we use somatic cell nuclear transfer to egg or oocyte to challenge the epigenetic mechanisms that are responsible for the stabilization of cell identity and resist the reprogramming of cell fate. By identifying these epigenetic mechanisms of resistance to change, we hope to improve reprogramming processes for therapeutical purposes as well as identify disruption in epigenetic mechanisms associated with ageing or diseases such as cancer.

3) Understanding human pre- and post-implantation development.

Despite 40 years of in vitro fertilization (IVF) practice in medicine, human development remains a black box. We are convinced that understanding human early development is a gateway to improve IVF. We are mapping molecular events with embryo morphological parameter in order to link clinical practice to fundamental research. We are currently extending the mapping up do 14 days post fertilisation and are adding proteomics analysis as an additional modality. In order to speed up our projects, mapped molecular events are used to generate a Boolean gene regulatory network, that could predict effect of perturbation on embryonic development. We now leverage all those approaches to modulate embryo culture conditions in order to improve IVF.

4) Leveraging stem cell models to study human early development.

The human embryo is our reference; however, investigations in this model are limited. To complement our analyses of human embryos, we have generated induced naïve pluripotent stem cells, induced trophoblast stem cells, and contributed to the generation of blastoids. We now use those models for mechanistic investigations of mechanism regulating cell fate, and to complement transcriptomics datasets with metabolic and proteomics analyses. A question that particularly interests us is to understand how the anterior visceral endoderm shapes the initiation of the body axis of the embryo.

5) Markers of IVF success

Nantes CHU has one of the French biggest reproductive biology department. Clinical data are routinely used to monitor and improve patient path. More specifically, we are performing proteomics analyses of culture media and deep learning analyses of morphokinetics parameters.

Platforms Managed by the Team

The iPSC Induced Pluripotent Stem Cell core facility

Led by Laurent David and supported by 6 technical staff, the iPSC Induced Pluripotent Stem Cell core facility is part of our local cluster of research (SFR). Its mission is to accelerate research in the stem cell field by facilitating the derivation and distribution of induced pluripotent stem (iPS) cell lines, genome editing, training and assisting partners in the setup of differentiation protocols. The platform is opened to local (45%), national (45%) or international (10%) users. R&D: the iPSC core facility has optimized differentiation and reprogramming protocols.

The Rat Transgenesis TRIP platform

Led by Jérôme Jullien and Matthieu Giraud, the TRIP platform generates genetically-modified rats. TRIP has a working force of 7 persons (ETP 3). TRIP services also include the distribution of rat models created for our own research but that also have widespread interest. Importantly, TRIP performs research and development on genome editing and transgenesis in the rat and other organisms as well as immunophenomic techniques.

Collaborators

Nicolas Rivron (IMBA, Vienna, AUT)
Charles Pineau (IRSET, Rennes, FR)
Hilde van de Velde (UZ Brussel, BEL)
Vincent Pasque (KU Leuven, BEL)
Peter Rugg-Gun (Babraham, Cambridge, UK)
Rita Vassena (EUGIN, Barcelona, SP)
Claire Rougeulle (Paris Cité, FR)
Claire Chazaud (GReD, Clermont-Ferrand, FR)
Anna Phillpott (CSCI, Cambridge, UK)
Estelle Marion (INCIT, Angers, FR)
Nathalie Beaujean (SBRI, Lyon, FR)
Romain Gibeaux (IGDR, Rennes,FR)

Grants

PEPR SAFE

Three projects from our team (2 coordinators, 1 as a partner) are part of this French consortium tackling infertility

ANR Research Grants

EPIPROSPECT: Epigenetic programming of the sperm chromatin
HU_BLAST: Shaping the human embryo for uterus implantation
BOOSTIVF: Improving IVF through integration of morphological and molecular analyses
CHROMNESS: Pluripotent stem cells in rabbits: manipulating epigenetic status to promote cell reprogramming and self-renewal stability

Regional Grant

Connect Talent: Epigenetic programming and reprogramming of cell fate

Research Scientists

Jérôme Jullien

DR2 INSERM

Laurent David

MCU-PH

Thomas Fréour

PU-PH

Harunobu Kagawa

CRCN INSERM

Associate Researchers

Djemil BENCHARIF - PU, DVM oniris
Lamia BRIAND AMIRAT - PU, DVM oniris
Pierre CALVEL - MCF Agroparitech

Clinicians

Sophie LOUBERSAC - MD, PH
Carole SPLINGART - PharmD, PH

Research assistants

Jenna LAMMERS - IH

Postdoctoral fellows

Vanessa QUILLAUD-CHENOUARD
Nolwenn MALTERRE

PhD students

Samuel BESSEAU
Florian BERGER
Simon CHEVOLLEAU
Manon FAUQUET
Océane GIRARD
Maïssa GOUMEIDANE
Eva MOINARD
Emilie ROCHARD

Mis à jour le 27 février 2025.