Unit 478
(End of project 2009)

Aims of the Research Unit:

The DFG Research Unit 478 “Mechanisms of embryo-maternal communication” has successfully entered the second funding period (2006-2008). An interdisciplinary team involving experts in embryology, biology of reproduction, biotechnology, and functional genome research was established and further developed to systematically dissect the embryo-maternal cross-talk in cattle in the pre-implantation period. This is achieved by bringing together optimized animal models (e.g. monozygotic twins) and cell culture systems with state-of-the-art techniques for transcriptome and proteome analysis, and bioinformatics.

Major achievements of the first funding period include (see also list of publications):

• Holistic transcriptome profiles and candidate gene characterization of oviduct epithelial cells and endometrium in various stages of the estrous cycle

• Optimized cell culture systems for oviduct epithelial cells and endometrial cells

• Holistic transcriptome profiles of oviduct epithelial cells after co-culture with embryos

• Holistic transcriptome and proteome profiles as well as candidate gene characterization of pregnant endometrium in the pre-attachment period in two independent in vivo models (cows after embryo transfer; heifers after artificial insemination)

• A custom made bovine oviduct endometrium (BOE) array with 900 identified transcripts

• New insights into the role of the extraembryonic matrix as a „mail box“ for signals in the embryo-maternal dialog

Based on these results the goals for the second funding period include an in-depth analysis of specific aspects of embryo-maternal communication using sophisticated experimental designs and analytical tools with markedly improved sensitivity. Specifically, we will address the following topics:

1. Investigation of position-dependent interactions with the endometrium by holistic transcriptome (Wolf/Blum/Reichenbach) and proteome studies (Arnold) using GFP-transgenic embryos

2. Characterization of interferon tau-specific effects on transcriptome profiles (Wolf/Blum/ Reichenbach) and proteome profiles (Arnold) in the endometrium.

3. Nuclear transfer embryos as a model for disturbed embryo-maternal interactions (transcriptome study: Wolf/Blum/Reichenbach, proteome study: Arnold).

4. Verification and functional validation of candidate genes identified in a-c is facilitated by the development of co-culture systems of embryos with oviduct or endometrium cells (Boelhauve/Hiendleder).

5. Mechanisms of embryo-maternal immune modulation will be characterized by RT-qPCR studies of candidate genes in endometrium and immune cells of the intrauterine fluid (Ulbrich/Meyer/Einspanier).

6. Holistic transcriptome analyses of various stages of in vivo derived vs. in vitro produced bovine embryos for monitoring embryonic development (Niemann/Adjaye).

7. First holistic proteome studies of preimplantation embryos using highly sensitive labeling techniques (Arnold).

8. Analysis of changes of nuclear architecture and the temporal/spatial occurrence of apoptosis in in vivo derived vs. in vitro produced embryos (Sinowatz/Habermann).

9. These experiments will provide a unique set of data for modeling the processes of embryo-maternal interaction and implantation using a systems biology approach.

The interactions between the individual projects are outlined in the following figure:

 

Coordinator:

Prof. Dr. Eckhard Wolf
Lehrstuhl für Molekulare Tierzucht und Biotechnologie
Genzentrum der Ludwig-Maximilians-Universität München
Feodor-Lynen-Strasse 25
81377 München
Phone: +49-89-2180-76800
Fax:      +49-89-2180-76849
ewolf@lmb.uni-muenchen.de