Rutgers geneticists have reported groundbreaking research on the genetics of fertility. They have discovered two genes, aptly named egg-1 and egg-2, required for fertilization to take place. The proteins encoded by these genes are similar to low density lipoprotein (LDL) receptors, known from cholesterol and fat metabolism but never before specifically implicated in fertilization. One in six couples is experiencing fertility problems worldwide, and people are asking why. This is a question of great medical, social and economic importance – one that cannot be answered until the process of fertilization is more fully understood. A team led by Andrew Singson, an assistant professor and Pavan Kadandale, a graduate student in the Singson lab at the Waksman Institute of Microbiology at Rutgers, The State University of New Jersey, has taken a new and productive approach in this quest. The researchers found that in the absence of these two genes, the vital process of fertilization came to a halt. “What we learn in studying fertilization is not only important for this event, but also for the functioning of other cells in our bodies and for understanding many of those processes,” Singson said. Fertilization can be a paradigm for gaining insight into how cells interact over the life and development of multicellular organisms because it is one of the most basic of cell-cell interactions. The underlying cell biology is going to be universal with applications even in infectious diseases, such as AIDS, where the virus passes its genetic material to the cells it infects just as fertilization transmits sperm DNA to the egg, Singson explained. Fertilization has primarily been studied in mammals or select marine invertebrates; but Singson and his group have instead turned to the lowly roundworm Caenorhabditis elegans (C. elegans), the first multicellular organism to have had its genome completely sequenced. In addition to having its genome sequence, C. elegans offers particular advantages as a model system – one from which results can be extrapolated to other organisms including humans. The millimeter-long worm is transparent, allowing a clear view of its internal workings, and its short life cycle permits researchers to chronicle developmental and hereditary factors over generations. These properties have enabled researchers to use C. elegans for fundamental discoveries in other fields ranging from cell death and life span regulation to nervous system structure and function. But the worm’s most important attribute as a model for this work may be its curious reproductive biology. Worms exist as males or hermaphrodites. When hermaphrodites are young they produce sperm and switch to produce eggs as adults. The Rutgers researchers were thus able to alter eggs in the hermaphrodites and use sperm from young males to test fertilization.
