Project Details
Projekt
Predictive molecular features of developmental competence in mouse embryos bisected at the 2-cell stage
Subject Area
Reproductive Medicine, Urology
Term
from 2010 to 2020
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 160013272
From 2011 to 2014 our two groups at MPI and CeRA joined strengths to investigate the effects of culture conditions on embryo quality in the mouse model of assisted reproductive technologies (ART). Unexpectedly, upon cleavage in culture media that are used in the clinics, fertilized mouse oocytes took on different developmental trajectories, characterized by medium-specific proportions of blastocysts and medium-specific patterns of gene expression. This renewal application to the DFG fosters new understanding of embryo development under in vitro conditions which are relevant to estimate any potential risks of ART procedures, and also provides clues to anticipate the outcome of ART procedures and to minimize the loss of oocytes and thereby the number of ART cycles. Our focus is on culture media, because they can reprogram cell fate in other fields of experimental biology; so, what about in ART?Given the heterogeneity of human embryos, until now it proved difficult to distinguish the contribution of the postfertilization culture environment from that of the intrinsic quality of the gametes (nature vs nurture). While it is utopic to mimic such heterogeneity in mice, it is feasible to eliminate it almost completely. Taking advantage of the method of mouse embryo bisection at the 2-cell stage, we can pursue the molecular traits that make a 2-cell embryo a developer or a non-developer under the provisions of a given environment (medium): after bisection, one cell provides the molecular information, which can be matched with the developmental information of the other cell. Further, we can use the two monozygotic twins to test if two different media elicit different developmental trajectories from the same genotype. From the bioinformatic comparison of the transcriptomes of twin embryos grown in different media we shall learn about the molecular transductors of environmental cues (extrinsic modulators of embryo quality e.g. signaling pathways). From the comparison of the transcriptomes of developmentally competent vs incompetent blastomeres across culture media we shall learn about the core of genes that are less sensitive to environmental cues.Our work can bring embryo research forward as the model of twinning will be applied to the study of ART culture media, leading to discover novel endpoints providing insight into the earliest stages of mammalian development. As in our previous DFG project, this renewal application will provide scientific evidence for critical steps of preimplantation development. Also, it should help to understand whether oocytes would be more suited for culture in a certain medium as opposed to another medium, after fertilization but before embryonic genome activation. Our collaborative enterprise between MPI and CeRA shall generate valid data to illuminate the earliest features of individuality in mammalian life.
DFG Programme
Research Grants
Co-Investigator
Professor Dr. Stefan Schlatt
