Programming the paternal nucleus for embryonic development

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One fascinating question in developmental biology is why fertilization almost invariably leads to the development of a very complex and defined organism. At fertilization two distinct highly specialised cells, the sperm and the egg, fuse to give rise to an embryo which can subsequently differentiate into numerous cell types that form an adult organism. But how does the embryo know which genes to switch on and when during the development in order to make these highly specialised cells? It turns out that the sperm may contain within its nucleus instruction to the embryo as to which genes to express and when. However, it is not well understood how the sperm is transmitting this information and what exactly is the nature of the information. Our research aims to understand how the sperm is prepared to deliver to the embryo information about gene expression and cell specialization. First, by comparing embryos derived from sperm and from sperm precursors, we have shown that the sperm-derived embryos develop 5 times better and are also better at transcribing genes than precursor-derived embryos. This means that the sperm acquires the information about correct embryonic gene expression during its maturation from the precursor. Now we want to find out what is the nature of this information by comparing components present on genes in sperm and sperm precursor cells and finding differences between them. Next, we want to see if this paternal information, embedded in the components present on genes, is still present in the embryos at the time of embryonic gene activation. To test directly the importance of the paternally-inherited information, we want to alter the way the components are associated with genes in the sperm and then monitor if the gene expression pattern in the embryo is altered. Last, we would like to find out if egg factors (the factors contributed from the mother) are important to read the paternal information. We believe that our results will have a significant impact on the field of regenerative medicine. For some human diseases/injuries there are currently no treatments applicable, other than a replacement with healthy cells. In order to generate cells for replacement therapies, differentiated cells have to be first switched back (reprogrammed) to an embryonic-like state. However, the frequency of reprogramming is very low. It is likely that this reprogramming inefficiency results from the fact that the somatic cell does not have the instructive information that is normally present in sperm and that dictates the expression of embryonic genes. If we know the nature of the information, one can then provide a somatic cell with such information in order to correct gene expression in reprogrammed cells, and therefore ultimately hope to increase the efficiency of derivation of cells for transplantation. Additionally, it has been shown that improper information about embryonic gene expression in the sperm can be associated with some cases of male infertility. Therefore, the outcome of our research may also help to prevent/treat male infertility cases.