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Embryonic origin of health and welfare: a new concept for understanding the susceptibility to diseases

Contract nr: FAIR-CT98-4339
Project nr: 4339
Project type: SC
Starting date: 01/01/1999
Duration: 24 months
Total cost: 1,687,852 EUR
EC Contribution: 1,017,891 EUR
Scientific Officer: Lucia PENA ALBERDI
Research topic: Animal Health

European husbandry contains animals that are decennia long selected for high production. Strict genetic selection for production seems to have lead to a reduced capability to adapt to the housing, the environment and the management. As a result, animal health and welfare seems to be seriously affected. The high yielding animals seem to have a reduced immune competence and are more vulnerable to infectious diseases. As a consequence, antibiotics and other therapeutics are increasingly used daily, bringing the livestock breeding industry into an unfavourable social climate. A new method, replacing the use of medicines, has to be found in order to solve these problems. This is only possible if we obtain more understanding of the origin of diseases and the susceptibility animals have to disease.

The objective of this research proposal is to gain information on altered patterns of development and gene expression. This gains insight into the origin of susceptibility to diseases and into resistance against infectious diseases. Such information is of vital importance to the development of future stategies to eliminate the problems of health and welfare without the use of medicines. Research will concentrate on gene activation in relation to tissue and organ development during early embryogenesis. The in vitro embryo production (IVP) system will be used as a model. It has been hypothesized that in this model the effect of the maternal and in vitro environment on all individual developmental stages, ranging from oocyte maturation to gastrulation of the embryonic tissue layers, can be separately studied and (cor)related to the health and welfare of the animal after birth.

The work programme brings together the various issues and approaches of the partners involved. They will study different stages of embryo development with complementary skills and facilities. They will compare in vivo with in vitro culture, with and without serum, synchronous with asynchronous transfer in order to have different conditions and environments for the developing embryo. This occurs along four well- defined lines, each subdivided into different tasks for the partners.
1. Morphological and cellular studies. Selection of cumulus-oocyte-complexes; Nuclear architecture and chromatin modification in early embryos; Differential staining of embryonic cells; Morphology of embryo compaction, blastocoel formation and differentiation of ectoderm, mesoderm and entoderm;
2. Biochemical, molecular and hormonal studies. Imprinted genes in oocytes and embryos. Housekeeping genes in embryogenesis; Analysis of one batch of serum. Protein content in embryos .
3. Developmental studies. Asynchronous embryo transfer; Synchronous transfers in different uterine environments.
4. Inventory of the consequences in vivo. Autopsies of fetus at 60 days (sheep) and 100 days (cattle): size and weight of organs; Measuring of types and amounts of immunoglobulins.

Current situation/results:
The project runs about officially one year. Since the whole project aimed to work together as soon as possible with the same culture protocol and even more important with the same serum batch, the attention was paid to select a serum that has proven to cause a high percentage of large calves with a few aberrations. That serum has been found.Transfers of embryos, in vitro produced in a system with this particular serum, have been started. Although the number of calves out of these embryos are always to few for a sound statistical analysis, the group decided nevertheless to continue embryo transferring till both 15 pregnancies from embryos cultured with and without serum are ongoing. The health of the calves will be studied intensively with special attention to their immuno resistance. When this serum has repeatedly proven to be responsible for a high percentage abnormalities, the serum will be analysed intensively for hormones and growth factors and all embryos cultured in the presence of this serum will be analysed on changes in expression of some imprinted, some housekeeping genes and other developmentally important genes related to organ development. Till that moment partners in the project try to make RT- PCR techniques as quantitative as possible and applicable to single oocytes/embryos. The results so far have shown that oocytes coming from differently classified follicles and differently qualified cumulus-oocyte-complexes differ in nuclear chromatin organisation and in H4 histon protein acetylation in the germinal vesicle stage and during the first hours of meiosis. From 6 hr after resumption of meiosis no differences between oocytes could be observed with these morphological parameters. After fertilization zygotes differed from each other again in acetylation grade of the histon proteins and in the length of the S phase of the first cell cycle before cleavage but this difference was more dominated by the origin of the sperm cell than by the differences between oocytes. It has been observed that the differences between in vivo and in vitro produced embryos concern the number of cells in the blastocyst stage at day 7 after fertilization and in the width and length of these embryos at day14. Differences between in vivo and in vitro produced embryos were also found for the glucose transporter 1 gene and the heat shock protein gene. How these differences can be related to abnormalities in the calves and in adult life has to be analysed. Answers to these questions can not be obtained before december of this year when the first calves will be born out of embryos cultured with the special serum as mentioned. In the coming month the research can be intensified when most tools to study gene expression related to culture conditions (environment) are developed, evaluated and available.

Theodoor A.M. KRUIP
Institute for Animal Science and Health
Edelhertweg 15
NL-8200 AB Lelystad
Tel.: +31 320 23 81 29
Fax: +31 320 23 80 50


  • Giovanna LAZZARI
    Consorzio per l'Incremento Zootecnico srl
    Via Maremmana 17 A/C
    I-56020 La Serra di S. Miniato
    Tel.: +39 03 72 43 72 42
    Fax: +39 03 72 43 61 33

  • Jean Paul RENARD
    Institut National de la Recherche Agronomique
    Rue de l'Université 147
    F-75338 Paris
    Tel.: +33 1 34 65 25 95
    Fax: +33 1 34 65 26 77

  • Ian WILMUT
    Roslin Institute (Edinburgh)
    UK-EH25 9PS Roslin
    Tel.: +44 1315 27 42 00
    Fax: +44 1314 40 04 34
    E-mail: Ian.Wilmut@Bbsrc.Ac.Uk

  • Heiner NIEMANN
    Institut Fuer Tierzucht Und Tierverhalten (Fal) Mariensee
    Höltystr. 10
    D-31535 Neustadt
    Tel.: +49 503 487 11 48
    Fax: +49 503 487 11 43
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