Department of Embryology and Genetics
The Research Department of Embryology and Genetics (EMGE) is linked to the Centres for Medical Genetics and Reproductive Medicine and the Department of Paediatrics of the UZ Brussel and consists of several research clusters. Historically, the group has been interested in metabolic diseases such as lysosomal storage diseases and this has led to the close collaboration with the neuro-paediatricians of the hospital, investigating mitochondrial diseases and their causes (L. De Meirleir, S. Seneca and W. Lissens). The research group on the genetic aspects of male infertility (W. Lissens) investigates the genetic causes for male infertility (eg maturation arrest of spermatogenesis or Sertoli cell-only syndrome) by using two different approaches: either through analysis of deletions on the Y-chromosome or through study of mutations in spermatogenesis-related genes, firstly on the X chromosome but also on autosomes. The research group on spermatogonial stem cells and spermatogenesis (H. Tournaye) investigates the possibilities of spermatogonial stem cell culture, storage and transplantation for treating chemotherapy-induced sterility or any other sterility caused by the loss or the lack of spermatogonial stem cells. A second research focus is the differentiation of human embryonic stem cells (hESC) into functional male gametes. Research into in-vitro differentiation of human embryonic cells to gametes can lead us to a better understanding of the causes of male infertility and may one day lead us to a new therapeutic approach to the treatment of male infertility. The research group on preimplantation genetic diagnosis (PGD) (I. Liebaers, K. Sermon, W. Lissens, M. De Rycke, C. Staessen) is an important combined clinical and research activity of the EMGE, which carries a great importance in terms of international significance. It is the skill and knowledge necessary to extract a correct and reliable diagnosis from as little as one or two cells that makes PGD such a challenge. The first PGDs in the early 90ies were for monogenic diseases such as cystic fibrosis and Duchenne's muscular dystrophy, using PCR technology to establish the diagnosis. Since a number of years now, the PGD team for monogenic diseases is led by M. De Rycke. In 1994, FISH technology at the single cell level was introduced by C. Staessen for gender selection of embryos when the mother carried an X-linked disease, and later also for the detection of chromosomal aberrations and aneuploidy screening. In 2007, 280 PCR-based PGDs for monogenic diseases were carried out, for over 50 different monogenic indications, including HLA typing, and 127 FISH-based diagnoses mainly for translocations. The close collaboration between the laboratory and the fertility clinic (P. Devroey) has also led to several papers on PGD from the clinical point of view. Other topics are (epi)genetics of the embryo, such as the behaviour of triplet repeat expansions or dynamic mutations in embryos (K. Sermon). Imprinting in gametes and embryos has been investigated by M. De Rycke as a means to evaluate the safety of ART procedures. In collaboration with J. De Grève, families with familial cancers such as BRCA1-related breast cancer are studied. Finally, the group around M. Bonduelle has a long track record in follow-up of children born after ART. The research on human embryonic stem cells (K. Sermon) is a novel activity at the EMGE since 2002. The derivation of human embryonic stem cell lines (hESC) from normal embryos and from embryos shown to be affected after PGD was our first point of interest. Currently, we have derived twenty-six stem cell lines, of which sixteen carry a monogenic disease. Other points of interest are (epi)genetic analysis of these cells, eg the behaviour of dynamic mutations, the identification of markers of totipotency that are common to embryos and HESC, the first differentiation step that occurs spontaneously which was shown to be an epithelial-mesenchymal transition (EMT), and finally the differentiation of stem cells into muscle (together with Prof. L. Leyns), lung tissue, insulin-producing cells (together with Prof. L. Bouwens) and bone and haematopoietic lineages (together with Prof. I. Van Riet and Prof. R. Cornelissen). The research group on clinical embryology (J. Van der Elst) focuses on optimisation of human embryo culture for selection of the single best embryo: testing new culture media, recombinant supplements, alternative culture methods (endometrial cells, uterine capsule) and new sperm selection methods. A second focus is cryopreservation of human gametes and embryos. Vitrification is studied as a superior freezing technique compared to the classical routinely used slow freezing. According to PubMed, CRG, CMG and EMGE have jointly published 815 papers since 1984, 364 of which were published in the period of 2000-2007.